2. Academic Validation
  3. Molecular mechanism of Gan-song Yin inhibiting the proliferation of renal tubular epithelial cells by regulating miR-21-5p in adipocyte exosomes

Molecular mechanism of Gan-song Yin inhibiting the proliferation of renal tubular epithelial cells by regulating miR-21-5p in adipocyte exosomes

  • J Ethnopharmacol. 2023 Dec 1:117530. doi: 10.1016/j.jep.2023.117530.
Duojie Xu 1,  Ling Yuan 2,  Mengying Che 1,  Doudou Lu 3,  Wenjing Liu 4,  Fandi Meng 1,  Yating Yang 1,  Yuhua Du 2,  Shaozhang Hou 5,  Yi Nan 6
Affiliations

Affiliations

  • 1 Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
  • 2 College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
  • 3 School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
  • 4 Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
  • 5 Key Laboratory of Craniocerebral Diseases, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
  • 6 Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan, 750004, Ningxia, China; Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, Ningxia, China. Electronic address: 20080011@nxmu.edu.cn.
PMID: 38043753 DOI: 10.1016/j.jep.2023.117530
Abstract

Ethnopharmacological relevance: Gan-song Yin is derived from the classic ancient prescription " Gan-song pill " for the treatment of wasting-thirst in Ningxia combined with the characteristic "fragrant medicine". It is clinically used for the treatment of early renal fibrosis caused by diabetic nephropathy. Previous studies have shown that it has a good effect and great potential in the prevention and treatment of diabetic nephropathy, but its mechanism research is still limited.

Aim of the study: To investigate the mechanism of GSY to improve DN by interfering with miR-21-5p and glycolipid metabolism in adipocyte exosomes using 3T3-L1 and TCMK-1 co-culture system.

Materials and methods: The co-culture system of 3T3-L3 and TCMK-1 was established, the IR model was established, and the stability, lipid drop change, glucose consumption, triglyceride content, cell viability, cell cycle and Apoptosis level, protein content and mRNA expression of the IR model were detected.

Results: GSY inhibited 3T3-L1 activity, increased glucose consumption and decreased TG content. Decreased TCMK-1 cell viability, inhibited Apoptosis, cell cycle arrest occurred in G0/G1 phase and S phase. Adipocyte IR model and co-culture system were stable within 48 h. After GSY intervention, lipid droplet decomposition and glucose consumption increased. The TG content of adipocytes increased, while the TG content of co-culture system decreased. GSY can regulate the expression of TGF-β1/SMAD signaling pathway protein in IR state. After GSY intervention, the expression of miR-21-5p was increased in 3T3-L1 and Exo cells, and decreased in TCMK-1 cells.

Conclusions: GSY can regulate TGF-β1/SMAD signaling pathway through the secretion of miR-21-5p from adipocytes, protect IR TCMK-1, regulate the protein and mRNA expression levels of PPARγ, GLUT4, FABP4, and improve glucose and lipid metabolism.

Keywords

Adipocytes; Co-culture system; Diabetic nephropathy; Exosomes; GSY; Renal tubular epithelial cells.

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