Journal
AUTOPHAGY
Volume 17, Issue 9, Pages 2586-2603Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2020.1821547
Keywords
Autophagy; colitis; exosomes; Mir7kmiRNA; mesenchymal stem cell; psychological stress
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Funding
- Guangdong Financial Fund for HighCaliber Hospital Construction [174-2018-XMZC-0001-03-0125]
- Pearl River Talent Recruitment Program [2019ZT08Y485]
- Sun Yat-sen University Young Teacher Key Cultivation Project [18ykzd05]
- National Nature Science Foundation of China [81970925]
- Program of China Scholarships Council [201606380078]
- Natural Science Foundation of Guangdong Province [2016A030313262]
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This study reveals a previously unknown role of autophagy in regulating MSCT therapy via exosomal miRNA Mir7k.
Mesenchymal stem cell transplantation (MSCT) has been applied to treat a variety of autoimmune and inflammatory diseases. Psychosocial stress can aggravate disease progression in chronic inflammatory patients. Whether psychological stress affects MSCT is largely unknown. In this study we show that psychological stress attenuates therapeutic effects of MSCT in a DSS-induced colitis mouse model by elevating the levels of exosomalMir7k/mmu-let-7 k(microRNA 7 k) in circulation. Mechanistically,Mir7kinhibits STAT3 pathway in donor MSCs, leading to upregulated expression of BECN1 (beclin 1, autophagy related) and, thus, activation of macroautophagy/autophagy. Inhibition of autophagy by blockingMir7kor activating STAT3 signaling can restore MSCT-mediated therapy in psychologically stressed colitis mice. Our study identifies a previously unknown role of autophagy in regulating MSCT therapyviaexosomal miRNAMir7k.
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