Galectin-3

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox gene}} '''Galectin-3''' is a protein that in humans is encoded by the ''LGALS3'' gene.<ref name="pmid2009535">{{cite journal | vauthors = Raz A, Carmi P, Raz T, Hogan V, Mohamed A, Wolman SR | title = Molecular cloning and chromosomal mapping of a human galactoside-binding protein | journal = Cancer Research | volume = 51 | issue = 8 | pages = 2173–8 | date = April 1991 | pmid = 2009535 }}</ref><ref name="pmid8063692">{{cite journal | vauthors = Barondes SH, Cooper DN, Gitt MA, Leffler H | title = Galectins. Structure and function of a large family of animal lectins | journal = The Journal of Biological Chemistry | volume = 269 | issue = 33 | pages = 20807–10 | date = August 1994 | doi = 10.1016/S0021-9258(17)31891-4 | pmid = 8063692 | doi-access = free }}</ref> Galectin-3 is a member of the lectin family, of which 14 mammalian galectins have been identified.<ref name=dumic>{{cite journal | vauthors = Dumic J, Dabelic S, Flögel M | title = Galectin-3: an open-ended story | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1760 | issue = 4 | pages = 616–35 | date = April 2006 | pmid = 16478649 | doi = 10.1016/j.bbagen.2005.12.020 }}</ref><ref name = "entrez">{{cite web | title = Entrez Gene: LGALS3 lectin, galactoside-binding, soluble, 3| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3958}}</ref>

Galectin-3 is approximately 30 kDa and, like all galectins, contains a carbohydrate-recognition-binding domain (CRD) of about 130 amino acids that enable the specific binding of β-galactosides.<ref name=dumic/><ref name=liu>{{cite journal | vauthors = Liu FT, Patterson RJ, Wang JL | title = Intracellular functions of galectins | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1572 | issue = 2–3 | pages = 263–73 | date = September 2002 | pmid = 12223274 | doi = 10.1016/S0304-4165(02)00313-6 | author-link1 = Fu-Tong Liu }}</ref><ref name=cooper>{{cite journal | vauthors = Cooper DN | title = Galectinomics: finding themes in complexity | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1572 | issue = 2–3 | pages = 209–31 | date = September 2002 | pmid = 12223271 | doi = 10.1016/S0304-4165(02)00310-0 }}</ref><ref name=henderson>{{cite journal | vauthors = Henderson NC, Sethi T | title = The regulation of inflammation by galectin-3 | journal = Immunological Reviews | volume = 230 | issue = 1 | pages = 160–71 | date = July 2009 | pmid = 19594635 | doi = 10.1111/j.1600-065X.2009.00794.x | s2cid = 36367366 }}.</ref>

Galectin-3 is also a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion, cell-matrix interactions, macrophage activation, angiogenesis, metastasis, apoptosis.

Galectin-3 is encoded by a single gene, LGALS3, located on chromosome 14, locus q21–q22.<ref name=dumic/><ref>{{cite journal | vauthors = Raimond J, Zimonjic DB, Mignon C, Mattei M, Popescu NC, Monsigny M, Legrand A | title = Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22 | journal = Mammalian Genome | volume = 8 | issue = 9 | pages = 706–7 | date = September 1997 | pmid = 9271684 | doi = 10.1007/s003359900548 | s2cid = 1955109 }}</ref> Galectin-3 is expressed in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space.<ref name=dumic/><ref name=liu/><ref name=cooper/>

== Function ==

Galectin-3 has an affinity for beta-galactosides and exhibits antimicrobial activity against bacteria and fungi.<ref name = "entrez"/>

This protein has been shown to be involved in the following biological processes: cell adhesion, cell activation and chemoattraction, cell growth and differentiation, cell cycle, and apoptosis.<ref name=dumic/> Given galectin-3's broad biological functionality, it has been demonstrated to be involved in cancer, inflammation and fibrosis, heart disease, and stroke.<ref name=dumic/><ref name=henderson/><ref name="Sharma_2004">{{cite journal | vauthors = Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, André S, Crijns HJ, Gabius HJ, Maessen J, Pinto YM | display-authors = 6 | title = Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction | journal = Circulation | volume = 110 | issue = 19 | pages = 3121–8 | date = November 2004 | pmid = 15520318 | doi = 10.1161/01.CIR.0000147181.65298.4D | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yan YP, Lang BT, Vemuganti R, Dempsey RJ | title = Galectin-3 mediates post-ischemic tissue remodeling | journal = Brain Research | volume = 1288 | pages = 116–24 | date = September 2009 | pmid = 19573520 | doi = 10.1016/j.brainres.2009.06.073 | s2cid = 8348013 }}</ref> Studies have also shown that the expression of galectin-3 is implicated in a variety of processes associated with heart failure, including myofibroblast proliferation, fibrogenesis, tissue repair, inflammation, and ventricular remodeling.<ref name="Sharma_2004"/><ref>{{cite journal | vauthors = Liu YH, D'Ambrosio M, Liao TD, Peng H, Rhaleb NE, Sharma U, André S, Gabius HJ, Carretero OA | display-authors = 6 | title = N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 296 | issue = 2 | pages = H404-12 | date = February 2009 | pmid = 19098114 | pmc = 2643891 | doi = 10.1152/ajpheart.00747.2008 }}</ref><ref>{{cite journal | vauthors = Lin YH, Lin LY, Wu YW, Chien KL, Lee CM, Hsu RB, Chao CL, Wang SS, Hsein YC, Liao LC, Ho YL, Chen MF | display-authors = 6 | title = The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 409 | issue = 1–2 | pages = 96–9 | date = November 2009 | pmid = 19747906 | doi = 10.1016/j.cca.2009.09.001 }}</ref>

Galectin-3 associates with the primary cilium and modulates renal cyst growth in congenital polycystic kidney disease.<ref name="pmid17148658">{{cite journal | vauthors = Chiu MG, Johnson TM, Woolf AS, Dahm-Vicker EM, Long DA, Guay-Woodford L, Hillman KA, Bawumia S, Venner K, Hughes RC, Poirier F, Winyard PJ | display-authors = 6 | title = Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease | journal = The American Journal of Pathology | volume = 169 | issue = 6 | pages = 1925–38 | date = December 2006 | pmid = 17148658 | pmc = 1762475 | doi = 10.2353/ajpath.2006.060245 }}</ref>

The functional roles of galectins in cellular response to membrane damage are rapidly expanding.<ref>{{cite journal | vauthors = Jia J, Abudu YP, Claude-Taupin A, Gu Y, Kumar S, Choi SW, Peters R, Mudd MH, Allers L, Salemi M, Phinney B, Johansen T, Deretic V | display-authors = 6 | title = Galectins Control mTOR in Response to Endomembrane Damage | journal = Molecular Cell | volume = 70 | issue = 1 | pages = 120–135.e8 | date = April 2018 | pmid = 29625033 | pmc = 5911935 | doi = 10.1016/j.molcel.2018.03.009 }}</ref><ref name="Jia_2020">{{cite journal | vauthors = Jia J, Claude-Taupin A, Gu Y, Choi SW, Peters R, Bissa B, Mudd MH, Allers L, Pallikkuth S, Lidke KA, Salemi M, Phinney B, Mari M, Reggiori F, Deretic V | display-authors = 6 | title = Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal | journal = Developmental Cell | volume = 52 | issue = 1 | pages = 69–87.e8 | date = January 2020 | pmid = 31813797 | doi = 10.1016/j.devcel.2019.10.025 | pmc = 6997950 }}</ref><ref>{{cite journal | vauthors = Jia J, Bissa B, Brecht L, Allers L, Choi SW, Gu Y, Zbinden M, Burge MR, Timmins G, Hallows K, Behrends C, Deretic V | display-authors = 6 | title = AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System | journal = Molecular Cell | pages = 951–969.e9 | date = January 2020 | volume = 77 | issue = 5 | pmid = 31995728 | doi = 10.1016/j.molcel.2019.12.028 | pmc = 7785494 }}</ref> It has been recently shown that galectin-3 recruits ESCRTs to damaged lysosomes so that lysosomes can be repaired.<ref name="Jia_2020" />

== Clinical significance ==

=== Early neurodevelopment ===

In early murine embryogenesis, galectin-3 is known to be expressed in the trophectoderm,<ref>{{Cite journal |last1=Colnot |first1=Céline |last2=Fowlis |first2=Deborah |last3=Ripoche |first3=Marie-Anne |last4=Bouchaert |first4=Isabelle |last5=Poirier |first5=Françoise |date=1998 |title=Embryonic implantation in galectin 1/galectin 3 double mutant mice |url=https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291097-0177%28199804%29211%3A4%3C306%3A%3AAID-AJA2%3E3.0.CO%3B2-L |journal=Developmental Dynamics |language=en |volume=211 |issue=4 |pages=306–313 |doi=10.1002/(SICI)1097-0177(199804)211:4<306::AID-AJA2>3.0.CO;2-L |issn=1097-0177|url-access=subscription }}</ref> notochord, and embryonic macrophages,<ref>{{Cite journal |last1=Fowlis |first1=D. |last2=Colnot |first2=C. |last3=Ripoche |first3=M. A. |last4=Poirier |first4=F. |date=June 1995 |title=Galectin-3 is expressed in the notochord, developing bones, and skin of the postimplantation mouse embryo |journal=Developmental Dynamics|volume=203 |issue=2 |pages=241–251 |doi=10.1002/aja.1002030211 |issn=1058-8388 |pmid=7655085}}</ref> but its functions in neurodevelopment remain unclear.<ref name=":0">{{Cite journal |last1=Soares |first1=Luana Campos |last2=Huang |first2=Ning |last3=Bernhardova |first3=Hana |last4=Macarelli |first4=Viviana |last5=Chan |first5=Marva |last6=Nikel |first6=Lara |last7=Bandiera |first7=Sara |last8=Yan |first8=Dongnan |last9=Gupta |first9=Dhanu |last10=Cruz |first10=Elisa M. |last11=Vasaturo-Kolodner |first11=Talia |last12=Hillis |first12=James M. |last13=Wood |first13=Matthew |last14=Salman |first14=Mootaz |last15=Molnár |first15=Zoltán |date=2025-09-03 |title=Galectin-3 induces neurodevelopmental apical-basal polarity and regulates gyrification |journal=Science Advances |volume=11 |issue=36 |article-number=eadt5859 |doi=10.1126/sciadv.adt5859 |pmc=12407091 |pmid=40901969}}</ref> Details as to how galectin-3 regulates murine neurogenesis continue to evolve. In the subventricular zone (SVZ), galectin-3 was shown to be important for neuroblast migration, acting possibly through an EGFR-based mechanism.<ref>{{Cite journal |last1=Comte |first1=Isabelle |last2=Kim |first2=Yongsoo |last3=Young |first3=Christopher C. |last4=van der Harg |first4=Judith M. |last5=Hockberger |first5=Philip |last6=Bolam |first6=Paul J. |last7=Poirier |first7=Françoise |last8=Szele |first8=Francis G. |date=2011-07-15 |title=Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb |journal=Journal of Cell Science |volume=124 |issue=Pt 14 |pages=2438–2447 |doi=10.1242/jcs.079954 |issn=1477-9137 |pmc=3124373 |pmid=21693585}}</ref> Galectin-3 has also been implicated in gliogenesis.<ref name=":0" /> In the postnatal ventricular subventricular zone (V-SVZ), galectin-3 expression was shown to be necessary for optimal gliogenesis, as reduced expression of galectin-3 led to a reduction in gliogenesis.<ref name=":1">{{Cite journal |last1=Al-Dalahmah |first1=Osama |last2=Campos Soares |first2=Luana |last3=Nicholson |first3=James |last4=Draijer |first4=Swip |last5=Mundim |first5=Mayara |last6=Lu |first6=Victor M. |last7=Sun |first7=Bin |last8=Tyler |first8=Teadora |last9=Adorján |first9=István |last10=O'Neill |first10=Eric |last11=Szele |first11=Francis G. |date=February 2020 |title=Galectin-3 modulates postnatal subventricular zone gliogenesis |journal=Glia |volume=68 |issue=2 |pages=435–450 |doi=10.1002/glia.23730 |issn=1098-1136 |pmc=6916335 |pmid=31626379}}</ref>

Galectin-3 expression levels also affect glia subpopulations differently. Increasing galectin-3 expression suppressed oligodendrogenesis and induced astrogenesis by virtue of BMP signaling.<ref name=":1" /> Galectin-3 binds BMPR1α and increases BMP signaling in the V-SVZ.<ref name=":1" /><ref name=":0" /> Galectin-3 also binds to β-catenin, an important component of adherens junctions,<ref>{{Cite journal |last1=Valenta |first1=Tomas |last2=Hausmann |first2=George |last3=Basler |first3=Konrad |date=2012-06-13 |title=The many faces and functions of β-catenin |journal=The EMBO Journal |volume=31 |issue=12 |pages=2714–2736 |doi=10.1038/emboj.2012.150 |issn=1460-2075 |pmc=3380220 |pmid=22617422}}</ref> potentially linking its activity to Wnt signaling pathways. Knockdown of galectin-3 increases Wnt signaling in the postnatal SVZ,<ref>{{Cite journal |last1=Al-Dalahmah |first1=Osama |last2=Nicholson |first2=James |last3=Draijer |first3=Swip |last4=Soares |first4=Luana Campos |last5=Szele |first5=Francis G. |date=September 2020 |title=Galectin-3 diminishes Wnt signaling in the postnatal subventricular zone |journal=Stem Cells |volume=38 |issue=9 |pages=1149–1158 |doi=10.1002/stem.3202 |issn=1549-4918 |pmid=32442340|doi-access=free }}</ref> furthering support for its potential involvement as a regulator or component of these pathways.

Galectin-3 expression has also been reported in stem cell niches of human and murine embryonic brain tissue, and has recently been revealed to play a role in the process of gyrification in the brain.<ref name=":0" /> Galectin-3 is necessary to establish apical-basal polarity (ABP) in human embryonic stem cells (hESCs) during neural differentiation,<ref name=":0" /> and galectin-3 inhibition disrupts the apical distribution of junctional complex proteins ''in vitro.''<ref name=":0" /> In fetal brains of female mice treated with galectin-3 inhibitors, the integrity of tight junctions in the ventricular zone (VZ) was lost, leading to early delamination of neural stem cells and increased vertical divisions.<ref name=":0" /> Unlike humans, the cerebral cortex of lower mammalian species such as mice do not have cortical folds (see gyri and sulci), but instead have lissencephalic cortices (''smooth brain'').<ref name=":0" /> Recently, it was reported that both pharmacological inhibition and genetic deletion of galectin-3 caused sulci to appear in the developing mouse cerebral cortex.<ref name=":0" />

=== Brain injury and stroke ===

Reactive glia are known to express galectin-3 in response to injury in the brain.<ref>{{Cite journal |last1=Bardella |first1=Chiara |last2=Al-Shammari |first2=Abeer R. |last3=Soares |first3=Luana |last4=Tomlinson |first4=Ian |last5=O'Neill |first5=Eric |last6=Szele |first6=Francis G. |date=November 2018 |title=The role of inflammation in subventricular zone cancer |journal=Progress in Neurobiology |volume=170 |pages=37–52 |doi=10.1016/j.pneurobio.2018.04.007 |issn=1873-5118 |pmid=29654835 |url=https://research.birmingham.ac.uk/portal/en/publications/the-role-of-inflammation-in-subventricular-zone-cancer(39b8b54d-f39a-4c79-82df-a60ebe395e7c).html }}</ref><ref>{{Cite journal |last1=Sirko |first1=Swetlana |last2=Schichor |first2=Christian |last3=Della Vecchia |first3=Patrizia |last4=Metzger |first4=Fabian |last5=Sonsalla |first5=Giovanna |last6=Simon |first6=Tatiana |last7=Bürkle |first7=Martina |last8=Kalpazidou |first8=Sofia |last9=Ninkovic |first9=Jovica |last10=Masserdotti |first10=Giacomo |last11=Sauniere |first11=Jean-Frederic |last12=Iacobelli |first12=Valentina |last13=Iacobelli |first13=Stefano |last14=Delbridge |first14=Claire |last15=Hauck |first15=Stefanie M. |date=December 2023 |title=Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain |journal=Nature Medicine |volume=29 |issue=12 |pages=3149–3161 |doi=10.1038/s41591-023-02644-6 |issn=1546-170X |pmc=10719094 |pmid=38066208}}</ref><ref>{{Cite journal |last1=Soares |first1=Luana C. |last2=Al-Dalahmah |first2=Osama |last3=Hillis |first3=James |last4=Young |first4=Christopher C. |last5=Asbed |first5=Isaiah |last6=Sakaguchi |first6=Masanori |last7=O'Neill |first7=Eric |last8=Szele |first8=Francis G. |date=2021-11-05 |title=Novel Galectin-3 Roles in Neurogenesis, Inflammation and Neurological Diseases |journal=Cells |volume=10 |issue=11 |page=3047 |doi=10.3390/cells10113047 |doi-access=free |issn=2073-4409 |pmc=8618878 |pmid=34831271}}</ref> Galectin-3 is reported as generally pro-inflammatory, and regulates angiogenesis and chemokine expression in models of stroke and disease.<ref name=":2">{{Cite journal |last1=Young |first1=Christopher C. |last2=Al-Dalahmah |first2=Osama |last3=Lewis |first3=Nicola J. |last4=Brooks |first4=Keith J. |last5=Jenkins |first5=Micaela M. |last6=Poirier |first6=Françoise |last7=Buchan |first7=Alastair M. |last8=Szele |first8=Francis G. |date=March 2014 |title=Blocked angiogenesis in Galectin-3 null mice does not alter cellular and behavioral recovery after middle cerebral artery occlusion stroke |journal=Neurobiology of Disease |volume=63 |pages=155–164 |doi=10.1016/j.nbd.2013.11.003 |issn=1095-953X |pmid=24269916}}</ref><ref>{{Cite journal |last1=James |first1=Rachel E. |last2=Hillis |first2=James |last3=Adorján |first3=István |last4=Gration |first4=Betty |last5=Mundim |first5=Mayara V. |last6=Iqbal |first6=Asif J. |last7=Majumdar |first7=Moon-Moon |last8=Yates |first8=Richard L. |last9=Richards |first9=Maureen M. H. |last10=Goings |first10=Gwendolyn E. |last11=DeLuca |first11=Gabriele C. |last12=Greaves |first12=David R. |last13=Miller |first13=Stephen D. |last14=Szele |first14=Francis G. |date=January 2016 |title=Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis |journal=Glia |volume=64 |issue=1 |pages=105–121 |doi=10.1002/glia.22906 |issn=1098-1136 |pmc=4988318 |pmid=26337870}}</ref><ref name=":0" /> In mice, modified citrus pectin was shown to prevent blood-brain barrier disruption in subarachnoid hemorrhage by inhibiting galectin-3.<ref>{{Cite journal |last1=Nishikawa |first1=Hirofumi |last2=Liu |first2=Lei |last3=Nakano |first3=Fumi |last4=Kawakita |first4=Fumihiro |last5=Kanamaru |first5=Hideki |last6=Nakatsuka |first6=Yoshinari |last7=Okada |first7=Takeshi |last8=Suzuki |first8=Hidenori |date=November 2018 |title=Modified Citrus Pectin Prevents Blood-Brain Barrier Disruption in Mouse Subarachnoid Hemorrhage by Inhibiting Galectin-3 |journal=Stroke |volume=49 |issue=11 |pages=2743–2751 |doi=10.1161/STROKEAHA.118.021757 |issn=1524-4628 |pmid=30355205}}</ref> It has also been shown that galectin-3 is necessary for vascular endothelial growth factor (VEGF)–dependent angiogenesis following mid cerebral artery occlusion stroke in mice.<ref name=":2" />

=== Fibrosis ===

A correlation between galectin-3 expression levels and various types of fibrosis has been found. Galectin-3 is upregulated in cases of liver fibrosis, renal fibrosis, and idiopathic pulmonary fibrosis (IPF). In several studies with mice deficient in or lacking galectin-3, conditions that caused control mice to develop IPF, renal, or liver fibrosis either induced limited fibrosis or failed to induce fibrosis entirely.<ref>{{cite journal | vauthors = Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T | display-authors = 6 | title = Galectin-3 regulates myofibroblast activation and hepatic fibrosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 13 | pages = 5060–5 | date = March 2006 | pmid = 16549783 | pmc = 1458794 | doi = 10.1073/pnas.0511167103 | bibcode = 2006PNAS..103.5060H | doi-access = free }}</ref><ref>{{cite journal | vauthors = Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, Liu FT, Hughes J, Sethi T | display-authors = 6 | title = Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis | journal = The American Journal of Pathology | volume = 172 | issue = 2 | pages = 288–98 | date = February 2008 | pmid = 18202187 | pmc = 2312353 | doi = 10.2353/ajpath.2008.070726 }}</ref><ref name="IPF">{{cite journal | vauthors = Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, Simpson AJ, Forbes SJ, Hirani N, Gauldie J, Sethi T | display-authors = 6 | title = Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3 | journal = American Journal of Respiratory and Critical Care Medicine | volume = 185 | issue = 5 | pages = 537–46 | date = March 2012 | pmid = 22095546 | pmc = 3410728 | doi = 10.1164/rccm.201106-0965OC }}</ref> Companies have developed galectin modulators that block the binding of galectins to carbohydrate structures. The galectin-3 inhibitors, TD139 and GR-MD-02 have the potential to treat fibrosis.<ref name="IPF" />

=== Cardiovascular disease ===

Elevated levels of galectin-3 have been found to be significantly associated with higher risk of death in both acute decompensated heart failure and chronic heart failure populations.<ref>{{cite journal | vauthors = van Kimmenade RR, Januzzi JL, Ellinor PT, Sharma UC, Bakker JA, Low AF, Martinez A, Crijns HJ, MacRae CA, Menheere PP, Pinto YM | display-authors = 6 | title = Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure | journal = Journal of the American College of Cardiology | volume = 48 | issue = 6 | pages = 1217–24 | date = September 2006 | pmid = 16979009 | doi = 10.1016/j.jacc.2006.03.061 | doi-access = free }}</ref><ref name="pmid20130888">{{cite journal | vauthors = Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, van Veldhuisen DJ | title = Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study | journal = Clinical Research in Cardiology | volume = 99 | issue = 5 | pages = 323–8 | date = May 2010 | pmid = 20130888 | pmc = 2858799 | doi = 10.1007/s00392-010-0125-y }}</ref> In normal human, murine, and rat cells galectin-3 levels are low. However, as heart disease progresses, significant upregulation of galectin-3 occurs in the myocardium.<ref>{{cite journal | vauthors = de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ | title = Galectin-3: a novel mediator of heart failure development and progression | journal = European Journal of Heart Failure | volume = 11 | issue = 9 | pages = 811–7 | date = September 2009 | pmid = 19648160 | doi = 10.1093/eurjhf/hfp097 | s2cid = 32686826 }}</ref>

Galectin-3 also may be used as a biomarker to identify at risk individuals, and predict patient response to different drugs and therapies. For instance, galectin-3 levels could be used in early detection of failure-prone hearts and lead to intervention strategies including broad spectrum anti-inflammatory agents.<ref name="Sharma_2004"/> One study concluded that individuals with systolic heart failure of ischaemic origin and elevated galectin-3 levels may benefit from statin treatment.<ref>{{cite journal | vauthors = Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, Adourian A, Böhm M, van Veldhuisen DJ, Komajda M, Cleland JG, Wikstrand J, McMurray JJ, Aukrust P | display-authors = 6 | title = Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) | journal = European Heart Journal | volume = 33 | issue = 18 | pages = 2290–6 | date = September 2012 | pmid = 22513778 | doi = 10.1093/eurheartj/ehs077 | doi-access = free }}</ref> Galectin-3 has also been associated as a factor promoting ventricular remodeling following mitral valve repair, and may identify patients requiring additional therapies to obtain beneficial reverse remodeling.<ref>{{cite journal | vauthors = Kortekaas KA, Hoogslag GE, de Boer RA, Dokter MM, Versteegh MI, Braun J, Marsan NA, Verwey HF, Delgado V, Schalij MJ, Klautz RJ | display-authors = 6 | title = Galectin-3 and left ventricular reverse remodelling after surgical mitral valve repair | journal = European Journal of Heart Failure | volume = 15 | issue = 9 | pages = 1011–8 | date = September 2013 | pmid = 23576289 | doi = 10.1093/eurjhf/hft056 | s2cid = 1252812 | doi-access = free }}</ref>

=== Cancer ===

The wide variety of effects of galectin-3 on cancerous cells are due to the unique structure and various interaction properties of the molecule. Overexpression and changes in the localization of galectin-3 molecules affects the prognosis of the patient and targeting the actions of galectin-3 poses a promising therapeutic strategy for the development of effective therapeutic agents for cancer treatment.

Overexpression and changes in sub- and inter-cellular localization of galectin-3 are commonly seen in cancerous conditions. The many interaction and binding properties of galectin-3 influence various cell activities based on its location. Altered galectin-3 expression can affect cancer cell growth and differentiation, chemoattraction, apoptosis, immunosuppression, angiogenesis, adhesion, invasion and metastasis.<ref name=Jack-of-all-trades>{{cite journal | vauthors = Newlaczyl AU, Yu LG | title = Galectin-3--a jack-of-all-trades in cancer | journal = Cancer Letters | volume = 313 | issue = 2 | pages = 123–8 | date = December 2011 | pmid = 21974805 | doi = 10.1016/j.canlet.2011.09.003 }}</ref>

Galectin-3 overexpression promotes neoplastic transformation and the maintenance of transformed phenotypes as well as enhances the tumour cell's adhesion to the extracellular matrix and increase metastatic spreading. Galectin-3 can be either an inhibitory or a promoting apoptotic depending on its sub-cellular localization. In immune regulation, galectin-3 can regulate immune cell activities and helps contribute to the tumour cell's evasion of the immune system. Galectin-3 also helps promote angiogenesis.<ref name=Jack-of-all-trades />

The roles of galectins and galectin-3, in particular, in cancer have been heavily investigated.<ref name=Liu>{{cite journal | vauthors = Liu FT, Rabinovich GA | title = Galectins as modulators of tumour progression | journal = Nature Reviews. Cancer | volume = 5 | issue = 1 | pages = 29–41 | date = January 2005 | pmid = 15630413 | doi = 10.1038/nrc1527 | s2cid = 4849835 | hdl = 11336/34814 | hdl-access = free }}</ref> Of note, galectin-3 has been suggested to play important roles in cancer metastasis.<ref name=Reticker-Flynn>{{cite journal | vauthors = Reticker-Flynn NE, Malta DF, Winslow MM, Lamar JM, Xu MJ, Underhill GH, Hynes RO, Jacks TE, Bhatia SN | display-authors = 6 | title = A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis | journal = Nature Communications | volume = 3 | issue = 3 | article-number = 1122 | year = 2012 | pmid = 23047680 | pmc = 3794716 | doi = 10.1038/ncomms2128 | bibcode = 2012NatCo...3.1122R }}</ref>

== Clinical applications ==

=== Cardiovascular risk indicator === Chronic heart failure has been found to be indicated by a galectin-3 tests, using the ARCHITECT immunochemistry platform developed by BG Medicine and marketed by Abbott, helping to determine which patients are most at risk for the disease. This test is also offered on the VIDAS platform marketed by bioMérieux.<ref>{{cite web|last=Ross|first=D|title=Abbott's Galectin-3 Test Provides Doctors in Europe with New Tool for Assessing the Prognosis of Chronic Heart Failure Patient|url=http://www.abbott.com/press-release/abbotts-galectin3-test-provides-doctors-in-europe-with-new-tool-for-assessing-the-prognosis-of-chr.htm|access-date=28 November 2013|archive-date=25 September 2013|archive-url=https://web.archive.org/web/20130925012641/http://www.abbott.com/press-release/abbotts-galectin3-test-provides-doctors-in-europe-with-new-tool-for-assessing-the-prognosis-of-chr.htm}}</ref> Pecta-Sol C binds to galectin-3 binding sites on the surfaces of cells as a preventative measure created by Isaac Eliaz in conjunction with EcoNugenics.<ref>{{cite journal|last=Brechka|first=Nicole | name-list-style = vanc |title=Putting the Squeeze on Cancer|year=2009|url=http://www.betternutrition.com/citrus-pectin-cancer-fighter/columns/favoritethings/1086|access-date=28 November 2013}}</ref>

Galectin-3 is upregulated in patients with idiopathic pulmonary fibrosis. The cells that receive galectin-3 stimulation (fibroblasts, epithelial cells, and myofibroblasts) upregulated the formation of fibrosis and collagen formation.<ref name = "yu" >{{cite journal | vauthors = Yu L, Ruifrok WP, Meissner M, Bos EM, van Goor H, Sanjabi B, van der Harst P, Pitt B, Goldstein IJ, Koerts JA, van Veldhuisen DJ, Bank RA, van Gilst WH, Silljé HH, de Boer RA | display-authors = 6 | title = Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis | journal = Circulation: Heart Failure | volume = 6 | issue = 1 | pages = 107–17 | date = January 2013 | pmid = 23230309 | doi = 10.1161/circheartfailure.112.971168 | doi-access = free }}</ref> Fibrosis is necessary in many aspects of intrabody regeneration. The myocardial lining constantly undergoes necessary fibrosis, and the inhibition of galectin-3 interferes with myocardial fibrogenesis. A study concluded that pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development.<ref name = "yu" />

=== Drug development ===

Galecto Biotech in Sweden is focused on developing drugs targeting galectin-3 to treat fibrosis, specifically idiopathic pulmonary fibrosis.<ref>{{cite journal | vauthors = Garber K | title = Galecto Biotech | journal = Nature Biotechnology | volume = 31 | issue = 6 | page = 481 | date = June 2013 | pmid = 23752421 | doi = 10.1038/nbt0613-481 | s2cid = 205268879 | doi-access = free }}</ref> Galectin Therapeutics in the United States is also targeting galectins for clinical applications. Preclinical studies demonstrate that inhibition of galectin-3 significantly reduces portal hypertension and fibrosis.<ref>{{cite web|title=Galectin Therapeutics' Preclinical Data Published in PLOS ONE Show Its Galectin Inhibitors Reverse Cirrhosis and Significantly Reduce Fibrosis and Portal Hypertension|url=http://phx.corporate-ir.net/phoenix.zhtml?c=135403&p=irol-newsArticle&ID=1863329&highlight=|publisher=Globe Newswire|access-date=28 November 2013}}</ref> In a phase 2b/3 trial, Galectin Therapeutics galectin-3 inhibitor belapectin reduces liver stiffness progression and prevents varices at 18 months in MASH cirrhosis.<ref>{{Cite news |title=Galectin Therapeutics to Present at the American Association for the Study of Liver Disease (AASLD) Liver Meeting 2025 |url=https://www.biospace.com/press-releases/galectin-therapeutics-to-present-at-the-american-association-for-the-study-of-liver-disease-aasld-liver-meeting-2025 |url-status=live |work=BioSpace}}</ref>. Earlier phase 1 data for belapectin also showed increased effectiveness and reduced side effects of cancer immunotherapy.<ref>{{cite journal | vauthors = Neuschwander-Tetri BA | title = Therapeutic Landscape for NAFLD in 2020 | journal = Gastroenterology | volume = 158 | issue = 7 | pages = 1984–1998.e3 | date = May 2020 | pmid = 32061596 | doi = 10.1053/j.gastro.2020.01.051 | s2cid = 211133881 }}</ref><ref>{{cite journal | vauthors = Narayan V, Thompson EW, Demissei B, Ho JE, Januzzi JL, Ky B | title = Mechanistic Biomarkers Informative of Both Cancer and Cardiovascular Disease: JACC State-of-the-Art Review | journal = Journal of the American College of Cardiology | volume = 75 | issue = 21 | pages = 2726–2737 | date = June 2020 | pmid = 32466889 | doi = 10.1016/j.jacc.2020.03.067 | pmc = 7261288 }}</ref><ref>{{cite journal | vauthors = Martínez-Bosch N, Rodriguez-Vida A, Juanpere N, Lloreta J, Rovira A, Albanell J, Bellmunt J, Navarro P | display-authors = 6 | title = Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities | journal = Nature Reviews. Urology | volume = 16 | issue = 7 | pages = 433–445 | date = July 2019 | pmid = 31015643 | doi = 10.1038/s41585-019-0183-5 | hdl = 10261/201560 | s2cid = 128360958 | hdl-access = free }}</ref>

=== Biomarkers ===

Galectin-3 is increasingly being used as a diagnostic marker for different cancers. It can be screened for and used as a prognostic factor to predict the progression of the cancer. Galectin-3 has varying effects in different types of cancer.<ref name="Galectin-3 biomarkers">{{cite journal | vauthors = Idikio HA | title = Galectin-3 and Beclin1/Atg6 genes in human cancers: using cDNA tissue panel, qRT-PCR, and logistic regression model to identify cancer cell biomarkers | journal = PLOS ONE | volume = 6 | issue = 10 | article-number = e26150 | date = 19 October 2011 | pmid = 22039439 | pmc = 3198435 | doi = 10.1371/journal.pone.0026150 | bibcode = 2011PLoSO...626150I | doi-access = free }}</ref> One approach to cancers with high galectin-3 expression is to inhibit galectin-3 to enhance treatment response.<ref>{{cite journal | vauthors = Cay T | title = {{sic|nolink=y|reason=error in source|Immunhistochemical}} expression of galectin-3 in cancer: a review of the literature | journal = Turk Patoloji Dergisi | volume = 28 | issue = 1 | pages = 1–10 | date = March 2011 | pmid = 22207425 | doi = 10.5146/tjpath.2012.01090 | series = 1 | doi-access = free }}</ref>

== Interactions ==

LGALS3 has been shown to interact with LGALS3BP.<ref name = pmid1917996>{{cite journal | vauthors = Rosenberg I, Cherayil BJ, Isselbacher KJ, Pillai S | title = Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin | journal = The Journal of Biological Chemistry | volume = 266 | issue = 28 | pages = 18731–6 | date = October 1991 | doi = 10.1016/S0021-9258(18)55124-3 | pmid = 1917996 | doi-access = free }}</ref><ref name = pmid8390986>{{cite journal | vauthors = Koths K, Taylor E, Halenbeck R, Casipit C, Wang A | title = Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain | journal = The Journal of Biological Chemistry | volume = 268 | issue = 19 | pages = 14245–9 | date = July 1993 | doi = 10.1016/S0021-9258(19)85233-X | pmid = 8390986 | doi-access = free }}</ref><ref name = pmid11146440>{{cite journal | vauthors = Tinari N, Kuwabara I, Huflejt ME, Shen PF, Iacobelli S, Liu FT | title = Glycoprotein 90K/MAC-2BP interacts with galectin-1 and mediates galectin-1-induced cell aggregation | journal = International Journal of Cancer | volume = 91 | issue = 2 | pages = 167–72 | date = January 2001 | pmid = 11146440 | doi = 10.1002/1097-0215(200002)9999:9999<::aid-ijc1022>3.3.co;2-q | doi-broken-date = 6 September 2025 }}</ref>

In melanocytic cells LGALS3 gene expression may be regulated by MITF.<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | display-authors = 6 | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–76 | date = December 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | s2cid = 24698373 | doi-access = free }}</ref>

== References== {{reflist|33em}}

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Category:Lectins