Роль катепсина S в патофизиологии бронхиальной астмы

До настоящего времени сохраняет свою актуальность изучение роли ферментов – протеаз в патогенезе различных заболеваний. Многообразие функций катепсинов обусловлено особенностями их локализации, экспрессии и регуляции, благодаря чему они принимают участие в развитии многих патологических процессов. Дисрегуляция активности протеаз, их ингибиторов и субстратов может привести к развитию полиорганных заболеваний.

В обзорной статье представлены данные о характеристике всего семейства катепсинов и катепсина S в частности; описаны его патофизиологические роли при формировании бронхолегочных патологий, а также при бронхиальной астме; освещены внутрии внеклеточные механизмы реализации. Авторы считают, именно этот фермент может стать мишенью для таргетной терапии астмы с целью предотвращения ремоделирования бронхиальной стенки на самых ранних этапах заболевания. Поиск литературы осуществлялся в поисковых системах Medline, еLibrary, Scopus, The Cochrane Library, РИНЦ.

1. Chang C.J., Chen C.C., Hsu L.A., Chang G.J., Ko Y.H., Chen C.F. et al. Degradation of the internal elastic laminae in vein grafts of rats with aortocaval fistulae: potential impact on graft vasculopathy. Am. J. Pathol. 2009;174(5):1837–1846. DOI: 10.2353/ajpath.2009.080795.

2. Lindholt J.S., Erlandsen E.J., Henneberg E.W. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br. J. Surg. 2001;88(11):1472–1475. DOI: 10.1046/j.0007-1323.2001.01911.x.

3. Chelladurai P., Seeger W., Pullamsetti S.S. Matrix metalloproteinases and their inhibitors in pulmonary hypertension. Eur. Respir. J. 2012;40(3):766–782. DOI: 10.1183/09031936. 00209911.

4. Hirakawa H., Pierce R.A., Bingol-Karakoc G., Karaaslan C., Weng M., Shi G.P. et al. Cathepsin S deficiency confers protection from neonatal hyperoxia-induced lung injury. Am. J. Respir. Crit. Care Med. 2007;176(8):778–785. DOI: 10.1164/rccm.200704-519OC.

5. Taggart C., Mall M.A., Lalmanach G., Cataldo D., Ludwig A., Janciauskiene S. et al. Protean proteases: at the cutting edge of lung diseases. Eur. Respir. J. 2017;49(2):1501200. DOI: 10.1183/13993003.01200-2015.

6. Leiberman J. Letter: familial variation of leukocyte lysosomal protease and serum alpha 1-antitrypsin as determinants in chronic obstructive pulmonary diseases. Am. Rev. Respir. Dis. 1973;108(4):1019–1020. DOI: 10.1164/arrd.1973.108.4.1019.

7. Lomas D.A. Does protease-Antiprotease imbalance ex plain chronic obstructive pulmonary disease? Ann. Am. Thorac. Soc. 2016;13(2):S130–137. DOI: 10.1513/AnnalsATS.201504-196KV.

8. Patel S., Homaei A., El-Seedi H.R., Akhtar N. Cathepsins: proteases that are vital for survival but can also be fatal. Biomed. Pharmacother. 2018;105:526–532. DOI: 10.1016/j.biopha.2018.05.148.

9. Garcia-Touchard A., Henry T.D., Sangiorgi G., Spagnoli L.G., Mauriello A., Conover C. et al. Extracellular proteases in atherosclerosis and restenosis. Arterioscler. Thromb. Vasc. Biol. 2005;25(6):1119–1127. DOI: 10.1161/01.ATV.0000164311.48592.da.

10. Yadati T., Houben T., Bitorina A., Shiri-Sverdlov R. The ins and outs of cathepsins: physiological function and role in disease management. Cells. 2020;9(7):1679. DOI: 10.3390/cells9071679.

11. Yan D., Wang H.W., Bowman R.L., Joyce J.A. STAT3 and STAT6 signaling pathways synergize to promote Cathepsin secretion from macrophages via IRE1alpha activation. Cell Rep. 2016;16(11):2914–2927. DOI: 10.1016/j.celrep.2016.08.035.

12. Wilkinson R.D., Williams R., Scott C.J., Burden R.E. Cathepsin S: therapeutic, diagnostic, and prognostic potential. Biol. Chem. 2015;396(8):867–882. DOI: 10.1515/hsz-2015-0114.

13. Caglic D., Repnik U., Jedeszko C., Kosec G., Miniejew C., Kindermann M. et al. The proinflammatory cytokines interleukin-1 α and tumor necrosis factor α promote the expression and secretion of proteolytically active cathepsin S from human chondrocytes. Biol. Chem. 2013;394(2):307–316. DOI: 10.1515/hsz-2012-0283.

14. Turk V., Stoka V., Vasiljeva O., Renko M., Sun T., Turk B. et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta. 2012;1824(1):68– 88. DOI: 10.1016/j.bbapap.2011.10.002.

15. Kaartinen M.T., Arora M., Heinonen S., Hang A., Barry A., Lundbom J. et al. F13A1 transglutaminase expression in human adipose tissue increases in acquired excess weight and associates with inflammatory status of adipocytes. Int. J. Obes. (Lond.). 2021;45(3):577–587. DOI: 10.1038/s41366020-00722-0.

16. Brown R., Nath S., Lora A., Samaha G., Elgamal Z., Kaiser R. et al. Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics. Respir. Res. 2020;21(1):111. DOI: 10.1186/s12931-02001381-5.

17. Geraghty P., Greene C.M., O’Mahony M., O’Neill S.J., Taggart C.C., McElvaney N.G. Secretory leucocyte protease inhibitor inhibits interferon-γ-induced cathepsin S expression. J. Biol. Chem. 2007;282(46):33389–33395. DOI: 10.1074/jbc. M706884200.

18. Barnes P.J. New therapies for chronic obstructive pulmonary disease. Med. Princ. Pract. 2010;19(5):330–338. DOI: 10.1159/000316368.

19. Wang Z., Zheng T., Zhu Z., Homer R.J., Riese R.J., Chapman Jr. H.A. et al. Interferon γ induction of pulmonary emphysema in the adult murine lung. J. Exp. Med. 2000;192(11):1587–1600. DOI: 10.1084/jem.192.11.1587.

20. Effros R.M., Chinard F.P. The in vivo pH of the extravascular space of the lung. J. Clin. Invest. 1969;48(11):1983–1996. DOI: 10.1172/JCI106164.

21. Vogelmeier C., Hubbard R.C., Fells G.A., Schnebli H.P., Thompson R.C., Fritz H. et al. Anti-neutrophil elastase defense of the normal human respiratory epithelial surface provided by the secretory leukoprotease inhibitor. J. Clin. Invest. 1991;87(2):482–488. DOI: 10.1172/JCI115021.

22. Wiedow O., Schroder J.M., Gregory H., Young J.A., Christophers E. Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J. Biol. Chem. 1990;265(25):14791–14795.

23. Twigg M.S., Brockbank S., Lowry P., FitzGerald S.P., Taggart C., Weldon S. The role of serine proteases and Antiproteases in the cystic fibrosis lung. Mediat. Inflamm. 2015;2015:293053 DOI: 10.1155/2015/293053.

24. Maciewicz R.A., Etherington D.J. A comparison of four cathepsins (B, L, N and S) with collagenolytic activity from rabbit spleen. Biochem. J. 1988;256(2):433–440. DOI: 10.1042/bj2560433.

25. Baugh M., Black D., Westwood P., Kinghorn E., McGregor K., Bruin J. et al. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity. J. Autoimmun. 2011;36(3-4):201–209. DOI: 10.1016/j.jaut.2011.01.003.

26. Font-Clos F., Zapperi S., La Porta C.A.M. Integrative analysis of pathway deregulation in obesity. NPJ Syst. Biol. Appl. 2017;3:18. DOI: 10.1038/s41540-017-0018-z.

27. Vidak E., Javorsek U., Vizovisek M., Turk B. Cysteine cathepsins and their extracellular roles: shaping the microenvironment. Cells. 2019;8(3):264. DOI: 10.3390/cells8030264.

28. Shi G.P., Webb A.C., Foster K.E., Knoll J.H., Lemere C.A., Munger J.S. et al. Human cathepsin S: chromosomal localization, gene structure, and tissue distribution. J. Biol. Chem. 1994;269(15):11530–11536.

29. Vizovisek M., Fonovic M., Turk B. Cysteine cathepsins in extracellular matrix remodeling: extracellular matrix degradation and beyond. Matrix Biol. 2019;7–576:141–159. DOI: 10.1016/j.matbio.2018.01.024.

30. Manchanda M., Fatima N., Chauhan S.S. Physiological and pathological functions of cysteine cathepsins. Proteases in physiology and pathology. Singapore, Springer, 2017:217– 256. DOI: 10.1007/978-981-10-2513-6_1135.

31. Naour N., Rouault C., Fellahi S., Lavoie M.E., Poitou C., Keophiphath M. et al. Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation. J. Clin. Endocrinol. Metab. 2010;95(4):1861–1868. DOI: 10.1210/jc.2009-1894.

32. Reddy V.B., Shimada S.G., Sikand P., Lamotte R.H., Lerner E.A. Cathepsin S elicits itch and signals via protease-activated receptors. J. Invest. Dermatol. 2010;130(5):1468–1470. DOI: 10.1038/jid.2009.430.

33. Jimenez-Vargas N.N., Pattison L.A., Zhao P., Lieu T., Latorre R., Jensen D.D. et al. Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome. Proc. Natl. Acad. Sci. USA. 2018;115(31):E7438–E7447. DOI: 10.1073/pnas.1721891115.

34. Beck H., Schwarz G., Schröte, C.J., Deeg M., Baier D., Stevanovic S. et al. Cathepsin S and an asparagine-specific endoprotease dominate the proteolytic processing of human myelin basic protein in vitro. Immunology. 2001;31(12):3726–3736. DOI: 10.1002/1521-4141(200112)31:12<3726::aid-immu3726> 3.0.co;2-o.

35. Lewis К., Kaufman J., Christakis N. The taste for privacy: an analysis of college student privacy settings in an online social network. J. Comput. Mediat. Commun. 2008;14(1):79–100. DOI: 10.1111/j.1083-6101.2008.01432.x.

36. Xu L., Feng B., Wang H., Li X. Multiple statistical methods for assessing differential gene expression in microarray data of diabetic model rats to predict the molecular mechanism of atorvastatin on anti-atherogenesis. Exp. Clin. Endocrinol. Diabetes. 2013;121(5):272–279. DOI: 10.1055/s-0033-1334955.

37. Zhao P., Lieu T., Barlow N., Metcalf M., Veldhuis N., Jensen D. et al. Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4. J. Biol. Chem. 2014;289(39):27215–27234. DOI: 10.1074/jbc.M114.599712.

38. Takayama F., Zhang X., Hayashi Y., Wu Z., Nakanishi H. Dysfunction in diurnal synaptic responses and social behavior abnormalities in cathepsin S-deficient mice. Biochem. Biophys. Res. Commun. 2017;490(2):447–452. DOI: 10.1016/j.bbrc.2017.06.061.

39. Elmariah S.B., Reddy V.B., Lerner E.A. Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist. PLoS One. 2014;9(6):e99702. DOI: 10.1371/journal.pone.0099702.

40. Jobs E., Adamsson V., Larsson A., Jobs M., Nerpin E., Ingelsson E. et al. Influence of a prudent diet on circulating cathepsin S in humans. Nutr. J. 2014;13:84. DOI: 10.1186/1475-289113-84.

41. Ahmad S., Bhagwati S., Kumar S., Banerjee D., Siddiqi M.I. Molecular modeling assisted identification and biolog ical evaluation of potent cathepsin S inhibitors. J. Biol. Chem. 2014;289(39):27215–27234. DOI: 10.1074/jbc.M114.599712.