PMID- 37594573
OWN - NLM
STAT- MEDLINE
DCOM- 20230821
LR  - 20230911
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 80
IP  - 9
DP  - 2023 Aug 18
TI  - Exosomes from TNF-alpha preconditioned human umbilical cord mesenchymal stromal cells 
      inhibit the autophagy of acinar cells of severe acute pancreatitis via shuttling 
      bioactive metabolites.
PG  - 257
LID - 10.1007/s00018-023-04861-1 [doi]
AB  - Severe acute pancreatitis (SAP) is a common critical disease of the digestive 
      system, with high mortality and a lack of effective 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-alpha-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 significantly 
      differentially expressed between the two groups (Exo-Ctrl group versus Exo-TNF-alpha 
      group). Then, the further functional experiments indicated that 
      3,4-dihydroxyphenylglycol could be a key molecule mediating the therapeutic 
      effect of TNF-alpha-preconditioned HUCMSCs. The animal experiments showed that 
      3,4-dihydroxyphenylglycol reduced inflammation 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-alpha-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.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Ma, Zhilong
AU  - Ma Z
AD  - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 
      270 Dong'An Road, Shanghai, 200032, China.
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
AD  - Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200050, China.
FAU - Xie, Wangcheng
AU  - Xie W
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
FAU - Luo, Tingyi
AU  - Luo T
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
FAU - Hu, Zhengyu
AU  - Hu Z
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
FAU - Hua, Jie
AU  - Hua J
AD  - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 
      270 Dong'An Road, Shanghai, 200032, China.
FAU - Zhou, Jia
AU  - Zhou J
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
AD  - Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200050, China.
FAU - Yang, Tingsong
AU  - Yang T
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 
      270 Dong'An Road, Shanghai, 200032, China.
FAU - Song, Zhenshun
AU  - Song Z
AD  - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji 
      University School of Medicine, Shanghai, 200072, China.
FAU - Yu, Xianjun
AU  - Yu X
AD  - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 
      270 Dong'An Road, Shanghai, 200032, China.
FAU - Xu, Jin
AU  - Xu J
AD  - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 
      270 Dong'An Road, Shanghai, 200032, China. xujin@fudanpci.org.
FAU - Shi, Si
AU  - Shi S
AUID- ORCID: 0000-0002-6652-0629
AD  - Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 
      270 Dong'An Road, Shanghai, 200032, China. shisi@fudanpci.org.
LA  - eng
GR  - 82200717/National Natural Science Foundation of China/
GR  - 81670582/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230818
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - UEH9K539KJ (3,4-dihydroxyphenylglycol)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Rats
MH  - *Pancreatitis/therapy
MH  - Acinar Cells
MH  - Tumor Necrosis Factor-alpha
MH  - Acute Disease
MH  - *Exosomes
MH  - *Mesenchymal Stem Cells
MH  - Autophagy
MH  - TOR Serine-Threonine Kinases
MH  - Umbilical Cord
OTO - NOTNLM
OT  - 3,4-Dihydroxyphenylglycol
OT  - Autophagy
OT  - Exosome
OT  - Mesenchymal stromal cell
OT  - Severe acute pancreatitis
EDAT- 2023/08/18 12:42
MHDA- 2023/08/21 06:42
CRDT- 2023/08/18 11:07
PHST- 2023/01/01 00:00 [received]
PHST- 2023/07/04 00:00 [accepted]
PHST- 2023/05/16 00:00 [revised]
PHST- 2023/08/21 06:42 [medline]
PHST- 2023/08/18 12:42 [pubmed]
PHST- 2023/08/18 11:07 [entrez]
AID - 10.1007/s00018-023-04861-1 [pii]
AID - 10.1007/s00018-023-04861-1 [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2023 Aug 18;80(9):257. doi: 10.1007/s00018-023-04861-1.