PMID- 37436133 OWN - NLM STAT- MEDLINE DCOM- 20230919 LR - 20230919 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 38 IP - 10 DP - 2023 Oct TI - Sinomenine improves renal fibrosis by regulating mesenchymal stem cell-derived exosomes and affecting autophagy levels. PG - 2524-2537 LID - 10.1002/tox.23890 [doi] AB - BACKGROUND: This study attempts to investigate the therapeutic effect of sinomenine on renal fibrosis and its mechanism. METHODS: The 8-week-old C57BL/6 male mice were randomly divided into sham group, UUO model group, UUO sinomenine group (UUO + Sino 50), UUO + sinomenine group (UUO + Sino 100), UUO + exosome group (exo), and UUO + exo-inhibitor. The pathological changes of kidney were observed by H&E staining, the degree of renal interstitial fibrosis was detected by MASSON and Sirius red staining, and the expressions of fibrosis and autophagy markers were detected by real-time fluorescence quantitative PCR and WB. NTA and electron microscopy were used to analyze exo secretion after sinomenine treatment. RESULTS: Sinomenine could improve the progression of renal fibrosis without causing tissue damage including heart, lungs and liver. Sinomenine could promote autophagosome formation. It could promote the secretion of exosomes from bone marrow mesenchymal stem cells (BMSCs). Sinomine regulates the PI3K-AKT pathway through BMSC-exo carrying miR-204-5p, affecting autophagy level and alleviating the process of renal fibrosis. CONCLUSION: Our study suggests that sinomine could improve the progression of renal fibrosis by influencing the expression of miR-204-5p in BMSC-exo and regulating the PI3K-AKT pathway. CI - (c) 2023 Wiley Periodicals LLC. FAU - Gu, Hongping AU - Gu H AD - Department of Internal Medicine, Yuyao Traditional Chinese Medicine Hospital, Yuyao, Zhejiang, China. FAU - Li, Jinrong AU - Li J AD - Department of Encephalopathy, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Ni, Yuehan AU - Ni Y AUID- ORCID: 0000-0002-9696-7077 AD - Department of Internal Medicine, Yuyao Traditional Chinese Medicine Hospital, Yuyao, Zhejiang, China. LA - eng GR - 2022-ZX04/The fourth round of Key Disciplines Construction Plan of Municipal and County Co-construction of TCM in Ningbo Integrated Traditional Chinese and Western Medicine Nephropathy Science/ GR - 2020YYB07/Yuyao City Health Science and Technology Plan Project/ PT - Journal Article DEP - 20230712 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - 63LT81K70N (sinomenine) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - 0 (MicroRNAs) SB - IM MH - Mice MH - Animals MH - Male MH - Proto-Oncogene Proteins c-akt/metabolism MH - *Exosomes/pathology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Mice, Inbred C57BL MH - *Kidney Diseases/metabolism MH - Fibrosis MH - Autophagy MH - *Mesenchymal Stem Cells/metabolism MH - *MicroRNAs/genetics/metabolism OTO - NOTNLM OT - autophagy OT - bone marrow mesenchymal stem cells OT - exosomes OT - miRNA OT - renal fibrosis OT - sinomenine EDAT- 2023/07/12 13:07 MHDA- 2023/09/19 06:42 CRDT- 2023/07/12 09:53 PHST- 2023/06/12 00:00 [revised] PHST- 2023/01/09 00:00 [received] PHST- 2023/06/29 00:00 [accepted] PHST- 2023/09/19 06:42 [medline] PHST- 2023/07/12 13:07 [pubmed] PHST- 2023/07/12 09:53 [entrez] AID - 10.1002/tox.23890 [doi] PST - ppublish SO - Environ Toxicol. 2023 Oct;38(10):2524-2537. doi: 10.1002/tox.23890. Epub 2023 Jul 12.