Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment

Stem Cell Research & Therapy

Ru-xing Wang²  Yanyun Zhang¹  Xiao-rong Li²  Zhen-yu Yang²  Ling-ling Qian²  Ying Wu²  Ku-lin Li²  Jie Zheng²  Chang-ying Zhang²  Zhi-ming Yu²  Shipeng Dang¹ 

[1] Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China;Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China

关键词: Bcl-2;    Sepsis;    Apoptosis;    Autophagy;    Mesenchymal stem cells;   

Others  :  1235599
DOI  :  10.1186/s13287-015-0245-4

 received in 2015-09-17, accepted in 2015-11-23,  发布年份 2015

【 摘 要 】

Background

Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified.

Methods

We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs.

Results

Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway.

Conclusions

Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.

【 授权许可】

   
2015 Dang et al.

【 图 表 】

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