nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2016-20-4-46-50nefr-189Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESГломерулярная гипертензия: молекулярные механизмы повреждения подоцитов и мезангиальных клетокGlomerular hypertension: molecular mechanisms of podocytes and mesangial cells damageКузьминОлег БорисовичKuzminO. B.kuzmin.orgma@mail.ruЖежаВладислав ВикторовичZhezhaVladislav V.zhezha56@mail.ruБелянинВиталий ВасильевичBelyaninVitaly V.vitbelya@yandex.ruЛандарьЛариса НиколаевнаLandarLarisa N.landar@mail.ruОренбургский государственный медицинский университетРоссияOrenburg State Medical UniversityRussian Federation2016010720162043139Copyright © Кузьмин О.Б., Жежа В.В., Белянин В.В., Ландарь Л.Н., 20162016Кузьмин О.Б., Жежа В.В., Белянин В.В., Ландарь Л.Н.Kuzmin O.B., Zhezha V.V., Belyanin V.V., Landar L.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/189

В обзоре представлены данные о молекулярных механизмах, лежащих в основе повреждения подоцитов и мезангиальных клеток клубочков при гломерулярной гипертензии. Механическое напряжение активирует в этих клетках локальные РАС и увеличивает выделение Анг II, который аутокринным и паракринным способом возбуждает АТ1-рецепторы и запускает сигнальные каскады, ведущие, в конечном итоге, к ЭМТ-подобным фенотипическим изменениям, апоптозу подоцитов и профибротическому перерождению мезангиальных клеток. Ключевую роль в этих процессах играет TGF-ß, который активирует сигнальные пути, опосредующие большинство патологических эффектов, возникающих в этих клетках при механическом повреждении и возбуждении АТ1-рецепторов их клеточных мембран. В низких концентрациях TGF-ß индуцирует в подоцитах Smad 2/3-зависимые и другие внутриклеточные каскады, которые вызывают ЭМТ-подобные изменения и дедифференцировку клеток, а в высоких концентрациях совместно с Анг II активирует сигнальные пути, ведущие к апоптозу и потере подоцитов в структуре гломерулярного фильтра. В мезангиальных клетках клубочков TGF-ß и Анг II запускают сигнальные пути, которые вызывают избыточную аккумуляцию мезангиального матрикса и стимулируют продукцию МСР-1, TNF-α, IL-18 и IL-6, индуцирующих воспаление мезангиальной ткани. Выяснение молекулярных механизмов повреждения подоцитов и мезангиальных клеток при гломерулярной гипертензии позволит выявить потенциальные мишени для разработки новых лекарственных препаратов для лечения гипертензивных больных с нефропатией различного происхождения.

The review presents data on the molecular mechanisms underlying podocytes and mesangial cells damage in glomerular hypertension. Mechanical stress in these cells activates the local RAS and increases the secretion of Ang II which in autocrine and paracrine manner stimulates AT1-receptors and triggers signaling cascades, leading eventually to the EMT-like phenotype changes, apoptosis podocytes and mesangial cells profibrotic degeneration. A key role in these processes plays a TGF-ß, which activates signaling pathways that mediate the majority of the pathological effects occuring in these cells upon mechanical damage and excitement of AT1-receptors of their cell membranes. At low concentrations TGF-ß induces in podocytes Smad 2/3-dependent and other intracellular signaling cascades which induce EMT-like changes and dedifferentiation of cells and at high concentrations together with Ang II activates signal pathways leading to apoptosis and loss of podocytes in glomerular filter structure. In glomerular mesangial cells TGF-ß and Ang II trigger signaling pathways which cause excessive accumulation of mesangial matrix and stimulate the production of MCP-1, TNFα, IL-18 and IL-6 inducing the inflammation of mesangial tissue. Elucidation of the molecular mechanisms of podocytes and mesangial cells damage in glomerular hypertension provides to identify potential targets for creation a new drugs development for the treatment of hypertensive patients with nephropathy of different origin.

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The authors declare that there are no conflicts of interest present.