Exendin-4 promotes paracrine action of adipose-derived stem cells through PI3K/Akt signaling pathways.
- Author:
Hao ZHOU
1
;
Junjie YANG
;
Jing WAGN
;
Shunying HU
;
Guanghui CHEN
;
Yundai CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Adipocytes; cytology; Animals; Cell Proliferation; Cells, Cultured; Chromones; Fibroblast Growth Factor 2; metabolism; Hepatocyte Growth Factor; metabolism; Insulin-Like Growth Factor I; metabolism; Morpholines; Peptides; pharmacology; Phosphatidylinositol 3-Kinases; metabolism; Proto-Oncogene Proteins c-akt; metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; Stem Cells; cytology; Up-Regulation; Vascular Endothelial Growth Factor A; metabolism; Venoms; pharmacology
- From: Journal of Southern Medical University 2014;34(10):1395-1401
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism by which exendin-4 promotes paracrine secretion of cytokines by adipose-derived stem cells (ADSCs).
METHODSIn vitro cultured SD rat ADSCs (fourth passage) with or without exendin-4 treatment underwent flow cytometry to characterize the surface markers. MTT assay was performed to assess the proliferation of the cells exposed to different concentrations (0-20 nm/L) of exendin-4, and the paracrine secretion of cytokines (bFGF, VEGF, HGF, and IGF-1) by the ADSCs was evaluated by qPCR. The changes in the expressions of p-Akt in the cells were analyzed by Western blotting and qPCR in response to exendin-4 (10 nm/L) with or without exposure to PI3K/Akt inhibitor LY-294002 (50 nm/L); bFGF, VEGF, HGF, and IGF-1 production in the cells were detected using ELISA kits.
RESULTSTreatment with exendin-4 for 12 h did not affect the surface marker profile of the ADSCs but promoted the cell proliferation (P<0.05). Exendin-4 significantly increased the mRNA expressions of VEGF, bFGF, HGF, and IGF-1 in a concentration-dependent manner, and 10 nm/L was the optimum concentration (P<0.05). Exendin-4 treatment resulted in significantly increased p-Akt expressions in the ADSCs, and PI3K/Akt inhibitor not only reversed such effects of exendin-4 on p-Akt but also diminished the exendin-4- mediated up-regulation of the paracrine cytokines.
CONCLUSIONExendin-4 can concentration-dependently promote the proliferative and paracrine capacities of ADSCs partially through the PI3K/Akt signaling pathway without affecting the surface marker profile of the cells.
