Гломерулярная гипертензия: молекулярные механизмы повреждения подоцитов и мезангиальных клеток

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.

гломерулярная гипертензия, подоциты, мезангиальные клетки, ангиотензин II, сигнальные пути

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