Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Dang, Shipeng; Yu, Zhi-ming; Zhang, Chang-ying; Zheng, Jie; Li, Ku-lin; Wu, Ying; Qian, Ling-ling; Yang, Zhen-yu; Li, Xiao-rong; Zhang, Yanyun; Wang, Ru-xing
• Is Part Of: Stem cell research & therapy. Volume 6:Issue 1(2015)
• Page Start: 1
• Page End: 9
• Publication Date: 2015-12
• Subjects: Mesenchymal stem cells -- Autophagy -- Apoptosis -- Sepsis -- Bcl-2; Stem cells -- Research -- Periodicals; Cellular therapy -- Periodicals; 616.0277405
• DOI: 10.1186/s13287-015-0245-4
• Languages: English
• ISSNs: 1757-6512

Abstract

Abstract 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 knockdownBeclin-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 geneBcl-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.