Н.Н. Зыбина1, О.В. Тихомирова2, Е.А. Куликова3, П.Л. Прищеп4, Н.Е. Кушлинский5

1–3 ФГБУ «Всероссийский центр экстренной и радиационной медицины им. А.М. Никифорова»
МЧС России (Санкт-Петербург, Россия)

4,5 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»
Минздрава России (Москва, Россия)

Постановка проблемы. Исследования последнего времени демонстрируют возможности галактозид-связывающих белков – галектинов как биомаркеров патологических процессов. Наибольший интерес в этом плане представляет галектин-3, высокие уровни которого ассоциированы с развитием фиброза при хронической сердечной недостаточности и, предположительно, могут быть использованы для стратификации риска пациентов с инфарктом миокарда. Вместе с тем, многие эффекты галектинов остаются не изученными и требуют системного анализа.

Цель работы – анализ данных современной литературы о роли галектинов различных классов в реализации фундаментальных механизмов клеточных функций и межклеточных взаимодействий при различных патологических состояниях и заболеваниях.

Результаты. Приведены данные о структуре и классификации семейства галектинов, их роли в активации, секреции цитокинов, клеточной миграции, пролиферации и апоптоза, а также во взаимодействии с межклеточным матриксом. Рассмотрены многообразные функции галектинов, которые обусловливают интерес исследователей к выявлению роли галектинов в патогенезе различных заболеваний и патологических состояний.

Практическая значимость. Выявление конкретных механизмов вовлечения галектинов в патогенез заболеваний, определение их диагностической и прогностической значимости может стать основой для их использования в качестве биомаркеров патологических процессов и мишени для терапевтического воздействия.

Зыбина Н.Н., Тихомирова О.В., Куликова Е.А., Прищеп П.Л., Кушлинский Н.Е. Галектины: характеристика, роль в патогенезе, клиническом течении и прогнозе заболеваний // Технологии живых систем. 2023. T. 20. № 2. С. 5-17. DOI: https://doi.org/ 10.18127/j20700997-202302-01

1. Leffler H. Galectin history, some stories, and some outstanding questions // Trends Glycosci. Glycotechnol. 2018. V. 30. № 172. P. SE129–SE135. DOI: 10.4052/tigg.1724.1SE.
2. Cummings R.D., Liu F.T. Galectins. Essential of glycobiology, second ed. 2009
3. van der Hoeven N.W., Hollander M.R., Yıldırımb C., et al. The emerging role of galectins in cardiovascular disease // Vascular Pharmacology. 2016. V. 81. P. 31-41. https://DOI.org/10.1016/j.vph.2016.02.006.
4. Hsieh S.H., Ying N.W., Wu M.H., et al. Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells // Oncogene. 2008. V. 27. № 26. P. 3746–3753. DOI: 10.1038/sj.onc.1211029
5. Thijssen V.L., Hulsmans S., Griffioen A.W. The Galectin Profile of the Endothelium: Altered Expression and Localization in Activated and Tumor Endothelial Cells // Am. J. Pathol. 2008. V.172. № 2. P. 545–553. DOI: 10.2353/ajpath.2008.070938
6. Chellan B., Narayani J., Appukuttan P.S. Galectin-1, an endogenous lectin produced by arterial cells, binds lipoprotein(a) [Lp(a)] in situ: Relevance to atherogenesis // Exp. Mol. Pathol. 2007. V. 83. № 3. P. 399-404. DOI: 10.1016/j.yexmp.2007.04.004
7. Sano H., Hsu L., Yu J.R., et al. Human Galectin-3 is a novel chemoattractant for monocytes and macrophages1 // J. Immunol. 2000. V. 165. № 4. P. 2156–2164. DOI: 10.4049/jimmunol.165.4.2156
8. Ozturk D., Celik O., Satilmis S., et al. Association between serum galectin-3 levels and coronary atherosclerosis and plaque burden/structure in patients with type 2 diabetes mellitus // Coronary Artery Disease. 2015. V. 26. № 5. Р. 396–401. DOI: 10.1097/MCA.0000000000000252
9. Yıldırım C., Vogel D.Y., Hollander M.R., et al. Galectin-2 Induces a Proinflammatory, AntiArteriogenic Phenotype in Monocytes and Macrophages // PLoS ONE. 2015. V. 10. № 4. P. e0124347. DOI: 10.1371/journal.pone.0124347
10. Paclik D., Werner L., Guckelberger О., et al. Galectins distinctively regulate central monocyte and macrophage function // Cell. Immunol. 2011. V. 271. Iss. 1. P. 97–103. DOI: 10.1016/j.cellimm.2011.06.003
11. Moiseeva E.P., Javed Q., Spring E.L., et al. Galectin 1 is involved in vascular smooth muscle cell proliferation // Cardiovascular Res. 2000. V. 45. № 2. P. 493–502. DOI: 10.1016/S0008-6363(99)00276-X
12. Grandin E.W., Jarolim P., Murphy S.A., et al. Galectin-3 and the Development of Heart Failure after Acute Coronary Syndrome: Pilot Experience from PROVE IT-TIMI 22 // Clin. Chem. 2012. V. 58. № 1. P. 267–273. DOI: 10.1373/clinchem.2011.174359
13. Ishibashi S., Kuroiwa T., Sakaguchi М., et al. Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke // Exp. Neurol. 2007. V. 207. № 2. P. 302–313. DOI: 10.1016/j.expneurol.2007.06.024
14. Nio-Kobayashi J., Itabashi T. Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions // Front. Neuroanat. 2021. V. 15. P. 767330. DOI: 10.3389/fnana.2021.767330
15. Wang X., Niub Y., Yuea C.-X., et al. Increased ileal bile acid binding protein and galectin-9 are associated with mild cognitive impairment and Alzheimer's disease // J. Psychiatr. Res. 2019. V. 119. P. 102–106. DOI: 10.1016/j.jpsychires.2019.10.002
16. Hernández E R., Sánchez-Maldonado C., Mayoral Chávez M.A., et al. The therapeutic potential of galectin-1 and galectin-3 in the treatment of neurodegenerative diseases // Expert. Rev. Neurother. 2020. V. 20. № 5. P. 439–448. DOI: 10.1080/14737175. 2020.1750955
17. Cengiz T., Türkboylarıb S., Gençlerc O. S., et al. The roles of galectin-3 and galectin-4 in the idiopatic Parkinson disease and its progression // Clinical Neurology and Neurosurgery. 2019. V. 184. Р. 105373. DOI: 10.1016/j.clineuro.2019.105373
18. Rabinovich G.A., Liu F.T., Hirashima M., et al. An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer // Scand. J. Immunol. 2007. V. 66. № 2-3. Р. 143–158.
    DOI: 10.1111/j.1365-3083.2007.01986.x
19. Cao Z.-Q., Guo X.-L. The role of galectin-4 in physiology and diseases // Protein Cell. 2016. V. 7. № 5. P. 314–324. DOI: 10.1007/s13238-016-0262-9
20. Waldner M.J., Neurath M.F. Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development // Semin. Immunol. 2014. V. 26. № 1. P. 75–79. DOI: 10.1016/j.smim.2013.12.003
21. Nishida A., Nagahama K., Imaeda H., et al. Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells // J. Exp. Med. 2012. V. 209. № 13. P. 2383–2394. DOI: 10.1084/jem.20112631
22. Niki T., Fujita K., Rosen H., et al. Plasma Galectin-9 Concentrations in Normal and Diseased Condition // Cell. Physiol. Biochem. 2018. V. 50. P. 1856–1868. DOI: 10.1159/000494866
23. Moar P., Tandon R. Galectin-9 as a biomarker of disease severity // Cell. Immunol. 2021. V. 361. P. 104287. DOI: 10.1016/j.cellimm.2021.104287
24. Sewgobind N.V., Albers S., Pieters R.J. Functions and inhibition of galectin-7, an emerging target in cellular pathophysiology // Biomolecules. 2021. V. 11. P. 1720–1745. DOI: 10.3390/biom11111720
25. Hara A., Niwa M., Noguchi K., et al. Galectin-3: A Potential Prognostic and Diagnostic Marker for Heart Disease and Detection of Early Stage Pathology // Biomolecules. 2020. V. 10. № 9. P. 1277–1295. DOI: 10.3390/biom10091277
26. Song X., Qiana X., Shen M., et al. Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression // Biochim. Biophys. Acta. 2015. V. 1853. № 2. P. 513–521. DOI: 10.1016/j.bbamcr.2014.12.001
27. Dumic J., Dabelic S., Flogel M. Galectin-3: An open-ended story // Biochim. Biophys. Acta. 2006. V. 1760. № 4. P. 616–635. DOI: 10.1016/j.bbagen.2005.12.020
28. Yu L., Ruifrok W.P., Meissner M., et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis // Circ. Heart Fail. 2013. V. 6. № 1. P. 107–117. DOI: 10.1161/CIRCHEARTFAILURE. 112.971168
29. Lõpez B., González A., Querejeta R., et al. Galectin-3 and histological, molecular and biochemical aspects of myocardial fibrosis in heart failure of hypertensive origin // Eur. J. Heart Fail. 2015 V. 17. P. 385–392. https://DOI.org/10.1002/ejhf.246 
30. Calvier L., Martinez-Martinez E., Miana M., et al. The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries // JACC. Heart Fail. 2015. V. 3. № 1. P. 59–67. DOI: 10.1016/j.jchf.2014.08.002
31. Meijers W.C., RogiervanderVelde A., Pascual-Figal D.A., et al. Galectin-3 and post-myocardial infarction cardiac remodeling // Eur. J. Pharmacol. 2015. V. 763. Pt A. P. 115–121. DOI: 10.1016/j.ejphar.2015.06.025
32. Liu Y.H., D’Ambrosio M., Liao T.D., et al. N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growthregulatory lectin // Am. J. Physiol. Heart Circ. Physiol. 2009. V. 296. P. H404–H412.
33. Slack R.J., Mills R., Mackinnon A.C. The therapeutic potential of galectin-3 inhibition in fibrotic disease // Int. J. Biochem. Cell. Biol. 2021. V. 130. P. 105881. DOI: 10.1016/j.biocel.2020.105881
34. Kolatsi-Joannou M., Price K.L., Winyard P.J., et al. Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury // PloS One. 2011. V. 6. № 4. P. e18683. DOI: 10.1371/journal.pone.0018683
35. de Boer R.A., van der Velde A.R., Mueller C., et al. Galectin-3: a modifiable risk factor in heart failure // Cardiovasc. Drugs Ther. 2014. V. 28. № 3. P. 237–246. DOI: 10.1007/s10557-014-6520-2
36. Frenay A.R., Yu L., van der Velde A.R., et al. Pharmacological inhibition of galectin-3 protects against hypertensive nephropathy // Am. J. Physiol. Renal Physiol. 2015. V. 308. № 5. P. F500–509. DOI: 10.1152/ajprenal.00461.2014
37. French B., Wang L., Ky B., et al. Prognostic Value of Galectin-3 for Adverse Outcomes in Chronic Heart Failure // J. Cardiac. Fail. 2016. V. 22. № 4. P. 256–262. DOI: 10.1016/j.cardfail.2015.10.022
38. Фёдорова Н.В., Кашталап В.В., Хрячкова О.Н., и др. Галектин-3 – перспективный биомаркер рискометрии при инфаркте миокарда с подъемом сегмента ST // Атеросклероз. 2015. Т. 11. № 4. С. 49–55.
39. Каретникова В.Н., Осокина А.В., Евсеева М.В., и др. Связь галектина сыворотки крови и дисфункции почек при инфаркте миокарда с подъемом сегмента ST // Кардиология. 2016. Т. 56. № 4. С. 25–31. DOI: 10.18565/cardio.2016.4.25-31
40. Saccon F., Gatto M., Ghirardello A., et al. Role of galectin-3 in autoimmune and non-autoimmune nephropathies // Autoimmun. Rev. 2017. V. 16. № 1. P. 34–47. DOI: 10.1016/j.autrev.2016.09.023
41. Zamora E., Lupón J., de Antonio M., et al. Renal function largely influences Galectin-3 prognostic value in heart failure // Int. J. Cardiol. 2014. V. 177. № 1. Р. 171–177. DOI: 10.1016/j.ijcard.2014.09.011
42. Milner T.D., Viner A.C., Mackinnon A.C., et al. Temporal expression of galectin-3 following myocardial infarction // Acta Cardiol. 2014. V. 69. № 6. P. 595–602. DOI: 10.1080/AC.69.6.1000001
43. Ho J.E., Liu С., Lyass А., et al. Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community // J. Am. College Cardiol. 2012. V. 60. № 14. P. 1249–1256. DOI: 10.1016/j.jacc.2012.04.053
44. Djoussé L., Matsumoto C., Petrone A., et al. Plasma galectin 3 and heart failure risk in the Physicians' Health Study // Eur. J. Heart Failure. 2014. V. 16. № 3. P. 350–354. DOI: 10.1002/ejhf.21
45. de Boer R.A., Lok D.J., Jaarsma T., et al. Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction // Ann. Med. 2011. V. 43. № 1. Р. 60–68. DOI: 10.3109/07853890.2010.538080
46. Chen A., Hou W., Zhang Y., et al. Prognostic value of serum galectin-3 in patients with heart failure: а meta-analysis // Int. J. Cardiol. 2015. V. 182. P. 168–170. DOI: 10.1016/j.ijcard.2014.12.137
47. de Boer R.A., Voors A.A., Muntendam P., et al. Galectin-3: a novel mediator of heart failure development and progression // Eur. J. Heart Fail. 2009. V. 11. № 9. P. 811–817. DOI: 10.1093/eurjhf/hfp097
48. Blanda V., Bracale U.M., Di Taranto M.D., et al. Galectin-3 in Cardiovascular Diseases // Int. J. Mol. Sci. 2020. V. 21. № 23. P. 9232–9250. DOI: 10.3390/ijms21239232
49. Meijers W.C., Januzzi J.L., deFilippi C., et al. Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: A pooled analysis of 3 clinical trials // Am. Heart J. 2014. V. 167. № 6. Р. 853–860.e4. DOI: 10.1016/j.ahj.2014.02.011
50. De Giusti C.J., Ure A.E., Rivadeneyra L., et al. Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis // J. Mol. Cell. Cardiol. 2015. V. 85. P. 58–70. DOI: 10.1016/j.yjmcc.2015.05.010
51. Varki A., Cummings R.D., Esko J.D., et al. (Eds.). Galectins. In Essentials of Glycobiology, 3rd; Cold Spring Harbor Laboratory Press: Cold Spring Harbor. NY. USA. 2015. P. 469–480.
52. Cervantes-Alvarez E., la Rosa N.L., la Mora M.S., et al. Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients // Sci. Rep. 2022. V. 12. № 1. P. 1856. DOI: 10.1038/s41598-022-05968-4
53. Caniglia J.L., Guda M.R., Asuthkar S., et al. A potential role for Galectin-3 inhibitors in the treatment of COVID-19 // Peer. J. 2020. V. 8. P. e9392. DOI: 10.7717/peerj.9392
54. Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins // Annu. Rev. Virol. 2016. V. 3. № 1. P. 237–261. DOI: 10.1146/annurev-virology-110615-042301
55. Burguillos M.A., Svensson M., Schulte T., et al. Microglia-Secreted galectin-3 acts as a toll-like receptor 4 ligand and contributes to microglial activation // Cell. Rep. 2015. V. 10. № 9. P. 1626–1638. DOI: 10.1016/j.celrep.2015.02.012
56. Doverhag C., Hedtjärn M., Poirier F., et al. Galectin-3 contributes to neonatal hypoxic-ischemic brain injury // Neurobiol. Dis. 2010. V. 38. № 1. Р. 36–46. DOI: 10.1016/j.nbd.2009.12.024
57. Wu L., Zhao Q., Zhu X., et al. A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain // Brain. Pathol. 2010. V. 20. № 6. Р. 1042–1054. DOI: 10.1111/j.1750-3639.2010.00410.x
58. Trompet S., Jukemaa W., P. Mooijaarte S., et al. Genetic variation in galectin-3 gene associates with cognitive function at old age // Neurobiol. Aging. 2012. V. 33. № 9. Р. 2232.e1–2232.e9. DOI: 10.1016/j.neurobiolaging.2012.05.001
59. Boza-Serrano A., Ruiz R., Sanchez-Varo R., et al. Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease // Acta Neuropathol. 2019. V. 138. № 2. P. 251–273. DOI: 10.1007/s00401-019-02013-z
60. Soares. L.C., Al-Dalahmah O., Hillis J., et al. Novel Galectin-3 Roles in Neurogenesis, Inflammation and Neurological Diseases // Cells. 2021. V. 10. № 11. P. 3047–3071. DOI: 0.3390/cells10113047
61. Lalancette-Hebert M., Swarup V., Beaulieu J.M., et al. Galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury // J. Neurosci. 2012. V. 32. № 30. P. 10383–10395. DOI: 10.1523/JNEUROSCI.1498-12.2012
62. Li P., Liu S., Lu M., et al. Hematopoietic derived galectin-3 causes cellular and systemic insulin resistance // Cell. 2016. V. 167. № 4. P. 973–984.e12. DOI: 10.1016/j.cell.2016.10.025
63. Mostacada K., Oliveira F.L., Villa-Verde D.M.S., et al. Lack of galectin-3 improves the functional outcome and tissue sparing by modulating inflammatory response after a compressive spinal cord injury // Exp. Neurol. 2015. V. 271. P. 390–400. DOI: 10.1016/ j.expneurol.2015.07.006
64. Pasmatzi E., Papadionysiou C., Monastirli A., et al. Galectin 3: an extraordinary multifunctional protein in dermatology. Сurrent knowledge and perspectives // An. Bras. Dermatol. 2019. V. 94. № 3. P. 348–354. DOI: 10.1590/abd1806-4841.20198426
65. Hara A., Niwa M., Noguchi K., et al. Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases // Biomolecules. 2020. V. 10. P. 389–408. DOI: 10.3390/biom10030389