Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Clinical and Experimental Pharmacology and Physiology - Tập 47 Số 3 - Trang 466-477 - 2020
Dayong Zhang1, Yifan Chen1, Xianbin Xu1, Haoyi Xiang1, Yizhan Shi1, Ying Gao1, Xiaowen Wang1, Xuefan Jiang2,3, Na Li1, Jianping Pan1
1Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, China
2Department of Otorhinolaryngology, Zhejiang Provincial People's Hospital, Hangzhou, China
3People 's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China

Tóm tắt

AbstractAutophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up‐ or down‐regulation of autophagy by using rapamycin (Rapa) or 3‐methyladenine, respectively, before MSC senescence induced by D‐galactose (D‐gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D‐gal and inhibited ROS generation. p‐Jun N‐terminal kinases (JNK) and p‐38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H2O2on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D‐gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagy‐delaying MSC senescence.

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Thông tin xuất bản

Clinical and Experimental Pharmacology and Physiology

Tập 47 Số 3

466-477

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