Exosomes from TNF‑α preconditioned human umbilical cord mesenchymal stromal cells inhibit the autophagy of acinar cells of severe acute pancreatitis via shuttling bioactive metabolites
机构：[1]Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, 200032, China.[2]Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.[3]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200050, China.
Severe acute pancreatitis (SAP) is a common critical disease of the digestive system, with high mortality and a lack of
efective prevention and treatment measures. Despite mesenchymal stromal cell transplantation having the potential to
treat SAP, its clinical application prospect is limited, and the mechanism is unclear. Here, we reveal the therapeutic role of
exosomes from TNF-α-preconditioned human umbilical cord mesenchymal stromal cells (HUCMSCs) in attenuating SAP
and show that it is partly dependent on exosomal metabolites. Bioactive metabolomics analysis showed that 48 metabolites
be signifcantly diferentially expressed between the two groups (Exo-Ctrl group versus Exo-TNF-α group). Then, the further
functional experiments indicated that 3,4-dihydroxyphenylglycol could be a key molecule mediating the therapeutic efect of
TNF-α-preconditioned HUCMSCs. The animal experiments showed that 3,4-dihydroxyphenylglycol reduced infammation
and oxidative stress in the pancreatic tissue and inhibited acinar cell autophagy in a rat model of SAP. Mechanistically, we
revealed that 3,4-dihydroxyphenylglycol activated the mTOR pathway to inhibit acinar cell autophagy and alleviate SAP.
In summary, our study demonstrated that exosomes from TNF-α-preconditioned HUMSCs inhibit the autophagy of acinar
cells of SAP by shuttling 3,4-dihydroxyphenylglycol and inhibiting the mTOR pathway. This study revealed the vital role and
therapeutic potential of metabolite-derived exosomes in SAP, providing a new promising method to prevent and therapy SAP.
基金：
Ethics Committee of Shanghai Tenth People’s Hospital, Tongji University School
of Medicine (SHDSYY-2022-2330).
第一作者机构：[1]Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, 200032, China.[2]Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.[3]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200050, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Ma Zhilong,Xie Wangcheng,Luo Tingyi,et al.Exosomes from TNF‑α preconditioned human umbilical cord mesenchymal stromal cells inhibit the autophagy of acinar cells of severe acute pancreatitis via shuttling bioactive metabolites[J].CELLULAR AND MOLECULAR LIFE SCIENCES.2023,80(9):doi:10.1007/s00018-023-04861-1.
APA：
Ma Zhilong,Xie Wangcheng,Luo Tingyi,Hu Zhengyu,Hua Jie...&Shi Si.(2023).Exosomes from TNF‑α preconditioned human umbilical cord mesenchymal stromal cells inhibit the autophagy of acinar cells of severe acute pancreatitis via shuttling bioactive metabolites.CELLULAR AND MOLECULAR LIFE SCIENCES,80,(9)
MLA：
Ma Zhilong,et al."Exosomes from TNF‑α preconditioned human umbilical cord mesenchymal stromal cells inhibit the autophagy of acinar cells of severe acute pancreatitis via shuttling bioactive metabolites".CELLULAR AND MOLECULAR LIFE SCIENCES 80..9(2023)
生物学