请输入您要查询的百科知识：

　

词条 Galectin-3
释义

  1. Function

  2. Clinical significance

      Fibrosis    Cardiovascular disease    Cancer  

  3. Clinical applications

      As an indicator of Cardiovascular Risk    Biomarkers  

  4. Interactions

  5. References

{{Infobox_gene}}Galectin-3 is a protein that in humans is encoded by the LGALS3 gene.[1][2] Galectin-3 is a member of the lectin family, of which 14 mammalian galectins have been identified.[3][4]

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.[3][5][6][7]

Galectin-3 (Gal-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.[3][8] Galectin-3 is expressed in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space.[3][5][6]

Function

Galectin-3 has an affinity for beta-galactosides and exhibits antimicrobial activity against bacteria and fungi.[4]

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.[3] Given galectin-3's broad biological functionality, it has been demonstrated to be involved in cancer, inflammation and fibrosis, heart disease, and stroke.[3][7][9][10] 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.[9][11][12]

Galectin-3 associates with the primary cilium and modulates renal cyst growth in congenital polycystic kidney disease.[13]

Clinical significance

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.[14][15][16] Companies have developed galectin modulators that block the binding of galectins to carbohydrate structures. The galectin-3 inhibitor, TD139 and GR-MD-02 have the potential to treat fibrosis.[16]

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.[17][18] 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.[19]

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.[9] One study concluded that individuals with systolic heart failure of ischaemic origin and elevated galectin-3 levels may benefit from statin treatment.[20] 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.[21]

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.[22]

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.[22]

The roles of galectins and galectin-3, in particular, in cancer have been heavily investigated.[23] Of note, galectin-3 has been suggested to play important roles in cancer metastasis.[24]

Clinical applications

As an indicator of Cardiovascular Risk

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.[25] 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.[26]

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.[27] 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 drugs binding to galectin-3 will benefit those who have too much fibrosis on the heart, but it might potentially backfire for those who need heart restructuring.[27]

Galecto Biotech is another research company focused on developing drugs using galectin-3 in treatment for fibrosis, specifically idiopathic pulmonary fibrosis.[28] Galectin Therapeutics in the United States is also using galectins for their research, finding recently that inhibition of galectin-3 significantly reduces portal hypertension and fibrosis in mice.[29]

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.[30] One approach to cancers with high galectin-3 expression is to use small molecule inhibition of galectin-3 to enhance treatment response.[31]

Interactions

LGALS3 has been shown to interact with LGALS3BP.[32][33][34]

In melanocytic cells LGALS3 gene expression may be regulated by MITF.[35]

References

1. ^{{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 | doi = }}
2. ^{{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 | pmid = 8063692 | doi = }}
3. ^1 2 3 4 5 {{cite journal | vauthors = Dumic J, Dabelic S, Flögel M | title = Galectin-3: an open-ended story | journal = Biochimica et Biophysica Acta | volume = 1760 | issue = 4 | pages = 616–35 | date = April 2006 | pmid = 16478649 | doi = 10.1016/j.bbagen.2005.12.020 }}
4. ^1 {{cite web | title = Entrez Gene: LGALS3 lectin, galactoside-binding, soluble, 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3958| accessdate = }}
5. ^1 {{cite journal|authorlink1=Fu-Tong Liu | vauthors = Liu FT, Patterson RJ, Wang JL | title = Intracellular functions of galectins | journal = Biochimica et Biophysica Acta | volume = 1572 | issue = 2–3 | pages = 263–73 | date = September 2002 | pmid = 12223274 | doi = 10.1016/S0304-4165(02)00313-6 }}
6. ^1 {{cite journal | vauthors = Cooper DN | title = Galectinomics: finding themes in complexity | journal = Biochimica et Biophysica Acta | volume = 1572 | issue = 2–3 | pages = 209–31 | date = September 2002 | pmid = 12223271 | doi = 10.1016/S0304-4165(02)00310-0 }}
7. ^1 {{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 }}.
8. ^{{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 }}
9. ^1 2 {{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 | 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 }}
10. ^{{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 }}
11. ^{{cite journal | vauthors = Liu YH, D'Ambrosio M, Liao TD, Peng H, Rhaleb NE, Sharma U, André S, Gabius HJ, Carretero OA | 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 }}
12. ^{{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 | 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 }}
13. ^{{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 | 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 }}
14. ^{{cite journal | vauthors = Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T | 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 }}
15. ^{{cite journal | vauthors = Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, Liu FT, Hughes J, Sethi T | 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 }}
16. ^1 {{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 | 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 }}
17. ^{{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 | 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 }}
18. ^{{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 }}
19. ^{{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 }}
20. ^{{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 | 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 }}
21. ^{{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 | 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 }}
22. ^1 {{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 }}
23. ^{{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 }}
24. ^{{cite journal | vauthors = Reticker-Flynn NE, Malta DF, Winslow MM, Lamar JM, Xu MJ, Underhill GH, Hynes RO, Jacks TE, Bhatia SN | title = A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis | journal = Nature Communications | volume = 3 | issue = 3 | pages = 1122 | year = 2012 | pmid = 23047680 | pmc = 3794716 | doi = 10.1038/ncomms2128 }}
25. ^{{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|accessdate=28 November 2013}}
26. ^{{cite journal|last=Brechka|first=Nicole|title=Putting the Squeeze on Cancer|year=2009|url=http://www.betternutrition.com/citrus-pectin-cancer-fighter/columns/favoritethings/1086|accessdate=28 November 2013}}
27. ^1 {{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 | 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 }}
28. ^{{cite journal | vauthors = Garber K | title = Galecto Biotech | journal = Nature Biotechnology | volume = 31 | issue = 6 | pages = 481 | date = June 2013 | pmid = 23752421 | doi = 10.1038/nbt0613-481 }}
29. ^{{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|accessdate=28 November 2013}}
30. ^{{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 | pages = e26150 | date = 19 October 2011 | pmid = 22039439 | doi = 10.1371/journal.pone.0026150 | url = http://pubmed.cn/22039439 | pmc=3198435}}
31. ^{{cite journal | vauthors = Cay T | title = Immunhistochemical expression of galectin-3 in cancer: a review of the literature | journal = Türk Patoloji Dergisi | volume = 28 | issue = 1 | pages = 1–10 | date = March 2011 | pmid = 22207425 | doi = 10.5146/tjpath.2012.01090 | series = 1 }}
32. ^{{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 | pmid = 1917996 | doi = }}
33. ^{{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 | pmid = 8390986 | doi = }}
34. ^{{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 }}
35. ^{{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 | 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 }}
{{PDB Gallery|geneid=3958}}{{NLM content}}

1 : Lectins
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/10 20:39:57