OBJECTIVE: To investigate the effect of semaglutide on high glucose-induced proliferation of cardiac fibroblasts (CFs) and explore its possible mechanism.
METHODS: Primary mouse CFs, identified by detecting vimentin expression, were stimulated with 25 mmol/L and treated with 5-20 nmol/L semaglutide, and the cell proliferation was examined with CKK-8 assay for concentration screening.Cultured CFs exposed to high glucose (25 mmol/L) were treated with 5 nmol/L semaglutide, and the changes in cell cycle were detected using Cell Cycle Staining Kit; The mRNA expressions of α-smooth muscle actin (α-SMA), transforming growth factor-β1(TGF-β1) and Smad3 were detected using RT-qPCR, and the levels of type Ⅰ collagen (CoLⅠ) and type Ⅲ collagen (CoLIII) in the cell cultures were determined with ELISA.
RESULTS: Compared with the control cells, the CFs cultured in high glucose exhibited significantly enhanced proliferative activity (<0.05) with increased percentage of S-phase cells.Semagutide treatment obviously inhibited high glucose-induced proliferation of the CFs (<0.05) and reduced the percentage of S-phase cells.High glucose stimulation significantly increased the mRNA expressions of α-SMA, CoL Ⅰ and CoLIII in the cells (<0.01), which were effectively lowered by semaglutide treatment (<0.01).The expressions of TGF-β1 and Smad3 were significantly increased in high glucose-stimulated CFs (<0.01) and were lowered by semaglutide treatment (<0.01).
CONCLUSION: Semaglutide can inhibit high glucose-induced proliferation and collagen synthesis in mouse CFs possibly by downregulating the TGFβ/Smad3 signaling pathway.