Mechanism of exosomes from adipose-derived mesenchymal stem cells on sepsis-induced acute lung injury by promoting TGF-β secretion in macrophages

• Published in: Surgery 2023-11, Vol.174 (5), p.1208-1219
• Main Authors: Chen, Yin, Wang, Lei, Liu, Mingzhao, Zhao, Jin, Xu, Xiangnan, Wei, Dong, Chen, Jingyu
• Format: Article
• Language: English
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2023.06.017

Acute lung injury (ALI) caused by sepsis is a life-threatening condition characterized by uncontrollable lung inflammation. The current study sought to investigate the mechanism of adipose-derived mesenchymal stem cell-derived exosomes (ADMSC-Exos) in attenuating sepsis-induced ALI through TGF-β secretion in macrophages. Adipose-derived mesenchymal stem cell-derived exosomes (ADMSC-Exos) were extracted from ADMSCs and identified. Septic ALI mouse models were established via cecal ligation and puncture (CLP), followed by administration of ADMSC-Exos or sh-TGF-β lentiviral vector. Mouse macrophages (cell line RAW 264.7) were treated with lipopolysaccharide (LPS), co-cultured with Exos and splenic T cells, and transfected with TGF-β siRNA. The lung injury of CLP mice was evaluated, and levels of inflammatory indicators and macrophage markers were measured. The localization of macrophage markers and TGF-β was determined, and the level of TGF-β in lung tissues was measured. The effect of TGF-β knockdown on sepsis-induced ALI in CLP mice was evaluated, and the percentages of CD4+CD25+Foxp3+ Tregs in mononuclear cells/macrophages and Foxp3 levels in lung tissues/co-cultured splenic T cells were examined. ADMSC-Exos were found to alleviate sepsis-induced ALI, inhibit inflammatory responses, and induce macrophages to secrete TGF-β in CLP mice. TGF-β silencing reversed the alleviating effect of ADMSC-Exos on sepsis-induced ALI. ADMSC-Exos also increased the number of Tregs in the spleen of CLP mice and promoted M2 polarization and TGF-β secretion in LPS-induced macrophages. After knockdown of TGF-β in macrophages in the co-culture system, the number of Tregs decreased, suggesting that ADMSC-Exos increased the Treg number by promoting macrophages to secrete TGF-β. Our findings suggest ADMSC-Exos can effectively alleviate sepsis-induced ALI in CLP mice by promoting TGF-β secretion in macrophages.