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Гломерулярная гипертензия: молекулярные механизмы повреждения подоцитов и мезангиальных клеток

https://doi.org/10.24884/1561-6274-2016-20-4-46-50

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Аннотация

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.

Об авторах

Олег Борисович Кузьмин
Оренбургский государственный медицинский университет
Россия


Владислав Викторович Жежа
Оренбургский государственный медицинский университет
Россия


Виталий Васильевич Белянин
Оренбургский государственный медицинский университет
Россия


Лариса Николаевна Ландарь
Оренбургский государственный медицинский университет
Россия


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Для цитирования:


Кузьмин О.Б., Жежа В.В., Белянин В.В., Ландарь Л.Н. Гломерулярная гипертензия: молекулярные механизмы повреждения подоцитов и мезангиальных клеток. Нефрология. 2016;20(4):31-39. https://doi.org/10.24884/1561-6274-2016-20-4-46-50

For citation:


Kuzmin O.B., Zhezha V.V., Belyanin V.V., Landar L.N. Glomerular hypertension: molecular mechanisms of podocytes and mesangial cells damage. Nephrology (Saint-Petersburg). 2016;20(4):31-39. (In Russ.) https://doi.org/10.24884/1561-6274-2016-20-4-46-50

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ISSN 1561-6274 (Print)
ISSN 2541-9439 (Online)