Статья
Мочекаменная болезнь (МКБ) – многофакторное заболевание обмена веществ, обусловленное взаимодействием генетических и средовых факторов. Изучение МКБ в настоящее время актуально в связи с неуклонным ростом заболеваемости и распространенности, а также высокой частотой рецидивов этой патологии. Большинство конкрементов при МКБ формируются на основе солей кальция. Для улучшения контроля над МКБ перспективным является исследование молекулярногенетических аспектов гиперкальциурии. В процессе реабсорбции кальция в почках важную роль играют клаудины – белки плотных контактов почечного эпителия.В обзоре представлены современные мировые данные об эпигенетической регуляции активности почечных клаудинов с помощью малых некодирующих РНК и перспективах использования компонентов системы «клаудины-микроРНК» для таргетной фармакотерапии МКБ. Статья содержит информацию о сегментно-специфической экспрессии клаудинов в нефронах, клаудинопатиях, связанных с нарушением обмена кальция в почках, плотных контактах как динамических равновесных системах, биогенезе и принципах действия микроРНК, различных терапевтических стратегиях с использованием микроРНК.
1. Zubkov I.V. [et al.] Epidemiology of urolithiasis and pilot study results concerning the use of extracorporeal shock wave lithotripsy. RMZh. 2021;29(8):7–10. (In Russ.) (Зубков И.В. [и др.]. Эпидемиология мочекаменной болезни и результаты пилотного исследования использования фиброкаликолитотрипсии // РМЖ. ‒ 2021. 29(8):7–10).
2. Vasudevan V. [et al.] The genetic framework for development of nephrolithiasis. Asian J Urol. 2017;4(1):18–26. doi: 10.1016/j.ajur.2016.11.003.
3. Gadzhiev N. [et al.] Urolithiasis prevalence in the Russian Federation: analysis of trends over a 15-year period. World J Urol. 2021;39(10):3939–3944. doi: 10.1007/s00345-021-03729-y.
4. Lang J. [et al.] Global trends in incidence and burden of urolithiasis from 1990 to 2019: an analysis of global burden of disease study data. Eur Urol Open Sci. 2022;35:37–46. doi: 10.1016/j.euros.2021.10.008.
5. Kalabekov A.A., Kazachenko A.V., Ivashchenko V.V. Risk factors of calcium and urate nephrolithiasis. Role of the canalicular dysfunction in stone formation. Jeksperimental'naja i klinicheskaja urologija. 2016;1:8–15. (In Russ.) (Калабеков А.А., Казаченко А.В., Иващенко В.В. Факторы риска кальциевого и уратного нефролитиаза. Роль канальцевых дисфункций в камнеобразовании. Экспериментальная и клиническая урология. ‒ 2016. ‒ №1. ‒ С. 8-15.
6. Spivacow F.R. [et al.] Kidney stones: composition, frequency and relation to metabolic diagnosis. Medicina (B Aires). 2016;76(6):343–348.
7. Tostivint I.N. [et al.] How useful is an oral calcium load test for diagnosing recurrent calcium stone formers? Urolithiasis. 2022;50(5):577–587. doi: 10.1007/s00240-022-01355-w.
8. Iskenderov B.G. Arterial hypertension and calcium metabolism. Penza.: NPO “Professional”. 2010; 224 p. (In Russ.) (Искендеров Б. Г. Артериальная гипертензия и метаболизм кальция. ‒ Пенза: НПО «Профессионал». ‒ 2010. ‒ 224 с.)
9. Zverev Ja.F. [et al.] Role of kidney in maintaining calcium and magnesium homeostasis and its disorders (Part I). Nefrologija i dializ. 2018;20(2):150–169. (In Russ.) (Зверев Я.Ф. [и др.]. Роль почек в поддержании кальциевого и магниевого гомеостаза и при его нарушениях (Ч. I). Нефрология и диализ. ‒ 2018. ‒ №20(2). ‒ С.150-169). doi: 10.28996/2618-9801-2018-2-150-169.
10. Parshina E.V. Renal tubular calcium transport, physiology and clinical significance: terra «cognita». Nefrologija i dializ. 2020;22(2):170–180. (In Russ.) (Паршина Е.В. Тубулярный транспорт кальция в почках, физиология и клиническое значение: terra «cognita». Нефрология и диализ. ‒ 2020. ‒ №22(2). ‒ С. 170-180). doi: 10.28996/2618-9801-2020-2-170-180.
11. Eftekhari A. [et al.] Cell junction proteins: crossing the glomerular filtration barrier in diabetic nephropathy. Int J Biol Macromol. 2020;148:475–482. doi: 10.1016/j.ijbiomac.2020.01.168.
12. Moor M.B., Bonny O. Ways of calcium reabsorption in the kidney. Am J Physiol Renal Physiol. 2016;310(11):F1337–F1350. doi: 10.1152/ajprenal.00273.2015.
13. Farquhar M.G., Palade G.E. Junctional complexes in various epithelia. J Cell Biol. 1963;17(2):375–412. doi: 10.1083/jcb.17.2.375.
14. Prot-Bertoye C., Houillier P. Claudins in renal physiology and pathology. Genes (Basel). 2020;11(3):290. doi: 10.3390/genes11030290.
15. Markov A.G. Claudins as tight junction proteins: the molecular element of paracellular transport. Rossijskij fiziologicheskij zhurnal im. I.M. Sechenova. 2013;99(2):175–195. (In Russ.) (Марков А.Г. Белки плотных контактов клаудины: молекулярное звено парацеллюлярного транспорта. Российский физиологический журнал им. И.М. Сеченова. ‒ 2013. ‒ №99(2). ‒ С. 175-195).
16. Furuse M. [et al.] Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141(7):1539–1550. doi: 10.1083/jcb.141.7.1539.
17. Taylor A. [et al.] Chimeric claudins: a new tool to study tight junction structure and function. Int J Mol Sci. 2021;22(9):4947. doi: 10.3390/ijms22094947.
18. Milatz S. A novel claudinopathy based on claudin-10 mutations. Int J Mol Sci. 2019;20(21):5396. doi: 10.3390/ijms20215396.
19. Fromm M. [et al.] Tight junctions of the proximal tubule and their channel proteins. Pflugers Arch. 2017;469(7–8):877–887. doi: 10.1007/s00424-017-2001-3.
20. Rubashkin A.A. [et al.] A theory of charge selectivity reversal in cationor anion-selective tight junctions between epithelial cells: a nonlocal electrostatic approach. Biophysics. 2021;66(1):84–90. doi: 10.1134/S0006350921010127.
21. Muto S. Physiological roles of claudins in kidney tubule paracellular transport. Am J Physiol Renal Physiol. 2017;312(1):F9–F24. doi: 10.1152/ajprenal.00204.2016.
22. Van Itallie C.M., Anderson J.M. The molecular physiology of tight junction pores. Physiology (Bethesda). 2004;19:331–338. doi: 10.1152/physiol.00027.2004.
23. Suzuki H. [et al.] Model for the architecture of claudin-based paracellular ion channels through tight junctions. J Mol Biol. 2015;427(2):291–297. doi: 10.1016/j.jmb.2014.10.020.
24. Heinemann U., Schuetz A. Structural Features of Tight-Junction Proteins. Int J Mol Sci. 2019;20(23):6020. doi: 10.3390/ijms20236020.
25. Tsukita S., Tanaka H., Tamura A. The claudins: from tight junctions to biological systems. Trends Biochem Sci. 2019;44(2):141–152. doi: 10.1016/j.tibs.2018.09.008.
26. Pyatchenkov M.O., Markov A.G., Rumyantsev A.Sh. Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part I. Nefrologija. 2022;26(1):10–26. (In Russ.) (Пятченков М.О., Марков А.Г., Румянцев А.Ш. Структурно-функциональные нарушения кишечного барьера и хроническая болезнь почек. Обзор литературы. Ч. I. Нефрология. ‒ 2022. – №26(1). ‒ С. 10-26). doi: 10.36485/1561-6274-2022-26-1-10-26.
27. Jo C.H., Kim S., Kim G.H. Claudins in kidney health and disease. Kidney Res Clin Pract. 2022;41(3):275–287. doi: 10.23876/j.krcp.21.279.
28. Yu A.S. Claudins and the kidney. J Am Soc Nephrol. 2015;26(1):11–19. doi: 10.1681/ASN.2014030284.
29. Plain A., Alexander R.T. Claudins and nephrolithiasis. Curr Opin Nephrol Hypertens. 2018;27(4):268–276. doi: 10.1097/MNH.0000000000000426.
30. Curry J.N. [et al.] Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease. J Clin Invest. 2020;130(4):1948–1960. doi: 10.1172/JCI127750.
31. Walsh S.V., Hopkins A.M., Nusrat A. Modulation of tight junction structure and function by cytokines. Adv Drug Deliv Rev. 2000;41(3):303–313. doi: 10.1016/s0169-409x(00)00048-x.
32. Soler A.P., Laughlin K.V., Mullin J.M. Effects of epidermal growth factor versus phorbol ester on kidney epithelial (LLC-PK1) tight junction permeability and cell division. Exp Cell Res. 1993;207(2):398–406. doi: 10.1006/excr.1993.1207.
33. Huang X. [et al.] Nanotopography enhances dynamic remodeling of tight junction proteins through cytosolic liquid complexes. ACS Nano. 2020;14(10):13192–13202. doi: 10.1021/acsnano.0c04866.
34. Sugimoto K., Chiba H. The claudin-transcription factor signaling pathway. Tissue Barriers. 2021;9(3):1908109. doi: 10.1080/21688370.2021.1908109.
35. Zhang L., Lu Q., Chang C. Epigenetics in Health and Disease. Adv Exp Med Biol. 2020;1253:3–55. doi: 10.1007/978-981-15-3449-2_1.
36. Lander E.S. [et al.] Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921. doi: 10.1038/35057062.
37. Xue Y., Chen R., Qu L., Cao X. Noncoding RNA: from dark matter to bright star. Sci China Life Sci. 2020;63(4):463–468. doi: 10.1007/s11427-020-1676-5.
38. Lee R.C., Feinbaum R.L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–854. doi: 10.1016/0092-8674(93)90529-y.
39. Alles J. [et al.] An estimate of the total number of true human miRNAs. Nucleic Acids Res. 2019;47(7):3353–3364. doi: 10.1093/nar/gkz097.
40. Pritchard C.C., Cheng H.H., Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012;13(5):358–369. doi: 10.1038/nrg3198.
41. Desvignes T. [et al.] miRNA nomenclature: a view incorporating genetic origins, biosynthetic pathways, and sequence variants. Trends Genet. 2015;31(11):613–626. doi: 10.1016/j.tig.2015.09.002.
42. Matsuyama H., Suzuki H.I. Systems and synthetic microRNA biology: from biogenesis to disease pathogenesis. Int J Mol Sci. 2019;21(1):132. doi: 10.3390/ijms21010132.
43. Saliminejad K. [et al.] An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol. 2019;234(5):5451–5465. doi: 10.1002/jcp.27486.
44. Lee C.H. [et al.] MicroRNA-regulated protein-protein interaction networks and their functions in breast cancer. Int J Mol Sci. 2013;14(6):11560–11606. doi: 10.3390/ijms140611560.
45. Riffo-Campos Á.L., Riquelme I., Brebi-Mieville P. Tools for sequence-based miRNA target prediction: what to choose? Int J Mol Sci. 2016;17(12):1987. doi: 10.3390/ijms17121987.
46. Tafrihi M., Hasheminasab E. MiRNAs: biology, biogenesis, their web-based tools, and databases. Microrna. 2019;8(1):4–27. doi: 10.2174/2211536607666180827111633.
47. Baker M.A. [et al.] Tissue-specific microRNA expression patterns in four types of kidney disease. J Am Soc Nephrol. 2017;28(10):2985–2992. doi: 10.1681/ASN.2016121280.
48. Winter J. [et al.] Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–234. doi: 10.1038/ncb0309-228.
49. Liang X. [et al.] LncRNA-miRNA-mRNA expression variation profile in the urine of calcium oxalate stone patients. BMC Med Genomics. 2019;12(1):57. doi: 10.1186/s12920-019-0502-y.
50. Wang B. [et al.] Analysis of altered microRNA expression profiles in proximal renal tubular cells in response to calcium oxalate monohydrate crystal adhesion: implications for kidney stone disease. PLoS One. 2014;9(7):e101306. doi: 10.1371/journal.pone.0101306.
51. Lu Y. [et al.] Integrative microRNA-gene expression network analysis in genetic hypercalciuric stone-forming rat kidney. PeerJ. 2016;4:e1884. doi: 10.7717/peerj.1884.
52. Lan C. [et al.] Integrative analysis of miRNA and mRNA expression profiles in calcium oxalate nephrolithiasis rat model. Biomed Res Int. 2017;2017:8306736. doi: 10.1155/2017/8306736.
53. Kriegel A.J., Mladinov D., Liang M. Translational study of microRNAs and its application in kidney disease and hypertension research. Clin Sci (Lond). 2012;122(10):439–447. doi: 10.1042/CS20110159.
54. D'Agata R., Spoto G. Advanced methods for microRNA biosensing: a problem-solving perspective. Anal Bioanal Chem. 2019;411(19):4425–4444. doi: 10.1007/s00216-019-01621-8.
55. Gong Y. [et al.] Epigenetic regulation of microRNAs controlling CLDN14 expression as a mechanism for renal calcium handling. J Am Soc Nephrol. 2015;26(3):663–676. doi: 10.1681/ASN.2014020129.
56. Gong Y., Hou J. Claudin-14 underlies Ca⁺⁺-sensing receptor-mediated Ca⁺⁺ metabolism via NFAT-microRNA-based mechanisms. J Am Soc Nephrol. 2014;25(4):745–760. doi: 10.1681/ASN.2013050553.
57. Hou J. Claudins and mineral metabolism. Curr Opin Nephrol Hypertens. 2016;25(4):308–313. doi: 10.1097/MNH.0000000000000239.
58. Hawkshaw N.J., Paus R. Beyond the NFAT Horizon: from cyclosporine A-induced adverse skin effects to novel therapeutics. Trends Pharmacol Sci. 2021;42(5):316–328. doi: 10.1016/j.tips.2021.02.001.
59. Gong Y. [et al.] Claudin-14 regulates renal Ca⁺⁺ transport in response to CaSR signalling via a novel microRNA pathway. EMBO J. 2012;31(8):1999–2012. doi: 10.1038/emboj.2012.49.
60. Dimke H. [et al.] Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Am J Physiol Renal Physiol. 2013;304(6):F761–F769. doi: 10.1152/ajprenal.00263.2012.
61. Hou J. Lecture: new light on the role of claudins in the kidney. Organogenesis. 2012;8(1):1–9. doi: 10.4161/org.19808.
62. Negri A.L. Role of claudins in renal calcium handling. Nefrologia. 2015;35(4):347–352. English, Spanish. doi: 10.1016/j.nefro.2015.06.011.
63. Negri A.L., Del Valle E.E. Role of claudins in idiopathic hypercalciuria and renal lithiasis. Int Urol Nephrol. 2022;54(9):2197–2204. doi: 10.1007/s11255-022-03119-2.
64. McDermott A.M. [et al.] The therapeutic potential of microRNAs: disease modulators and drug targets. Pharm Res. 2011;28(12):3016– 3029. doi: 10.1007/s11095-011-0550-2.
65. Zhao X. [et al.] Tight junctions and their regulation by non-coding RNAs. Int J Biol Sci. 2021;17(3):712–727. doi: 10.7150/ijbs.45885.
66. Beermann J. [et al.] Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev. 2016;96(4):1297–1325. doi: 10.1152/physrev.00041.2015.
67. Bernardo B.C. [et al.] miRNA therapeutics: a new class of drugs with potential therapeutic applications in the heart. Future Med Chem. 2015;7(13):1771–1792. doi: 10.4155/fmc.15.107.
68. George J., Patel T. Noncoding RNA as therapeutic targets for hepatocellular carcinoma. Semin Liver Dis. 2015;35(1):63–74. doi: 10.1055/s-0034-1397350.
69. Beyer S., Fleming J., Meng W. [et al.] The role of miRNAs in angiogenesis, invasion and metabolism and their therapeutic implications in gliomas. Cancers (Basel). 2017;9(7):85. doi: 10.3390/cancers9070085.
70. Chen Z. [et al.] Pioglitazone decreased renal calcium oxalate crystal formation by suppressing M1 macrophage polarization via the PPAR-γ-miR-23 axis. Am J Physiol Renal Physiol. 2019;317(1):F137–F151. doi: 10.1152/ajprenal.00047.2019.
71. Brunner J., Ragupathy S., Borchard G. Target specific tight junction modulators. Adv Drug Deliv Rev. 2021;171:266–288. doi: 10.1016/j.addr.2021.02.008.
72. Hashimoto Y. [et al.] Anti-claudin antibodies as a concept for development of claudin-directed drugs. J Pharmacol Exp Ther. 2019;368(2):179–186. doi: 10.1124/jpet.118.252361.
73. Singh P., Toom S., Huang Y. Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer. J Hematol Oncol. 2017;10(1):105. doi: 10.1186/s13045-017-0473-4.
74. Li J. Targeting claudins in cancer: diagnosis, prognosis and therapy. Am J Cancer Res. 2021;11(7):3406–3424.
75. Wang X. [et al.] Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma. World J Gastrointest Oncol. 2022;14(7):1252–1264. doi: 10.4251/wjgo.v14.i7.1252.
76. Wong Y. [et al.] Metabolic syndrome and kidney stone disease: a systematic review of literature. J Endourol. 2016;30(3):246–253. doi: 10.1089/end.2015.0567.
77. Gajiyev N.K. [et al.] Urolithiasis and metabolic syndrome. Pathophysiology of stone formation. Jeksperimental'naja i klinicheskaja urologija. 2018;1:66–75. (In Russ.) (Гаджиев Н.К. [и др.]. Мочекаменная болезнь и метаболический синдром. Патофизиология камнеобразования. Экспериментальная и клиническая урология. ‒2018. ‒ №1. ‒ С. 66-75).
78. Derkach I.A. The role of intestines in the development of urolithiasis. Novosti mediciny i farmacii. 2015;1(527):33–37. (In Russ.) (Деркач И.А. Значение кишечника в развитии уролитиаза. Новости медицины и фармации. ‒ 2015. ‒ №1(527). ‒ С. 33-37).
79. Kazmirchuk A.V. [et al.] Role of immune status and redox potential in the pathogenesis of secondary pyelonephritis on the background of urolithiasis. Sovremennye problemy nauki i obrazovanija. 2016;3:65. (In Russ.) (Казмирчук А.В. [и др.] Роль иммунного статуса редокс-потенциала в патогенезе вторичного пиелонефрита при мочекаменной болезни. Современные проблемы науки и образования. ‒ 2016. ‒ №3. ‒ С. 65).
80. Saenko V.S., Pesegov S.V. Interdisciplinary approach for prevention of recurrent urinary stone disease. Urologija. 2020;5:87–92. (In Russ.) (Саенко В.С., Песегов С.В. Междисциплинарный подход к профилактике рецидивов мочекаменной болезни. Урология. ‒ 2020. ‒ №5. ‒ С. 87-92). doi: 10.18565/urology.2020.5.87-92.
81. Fu X., Dong D. Bioinformatic analysis of microRNA sequencing data. Methods Mol Biol. 2018;1751:109–125. doi: 10.1007/978-14939-7710-9_8.
