Abstract: 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 (P<0.05) with increased percentage of S-phase cells. Semagutide treatment obviously inhibited high glucose-induced proliferation of the CFs (P<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 (P<0.01), which were effectively lowered by semaglutide treatment (P<0.01). The expressions of TGF-β1 and Smad3 were significantly increased in high glucose-stimulated CFs (P<0.01) and were lowered by semaglutide treatment (P<0.01). Conclusion Semaglutide can inhibit high glucose-induced proliferation and collagen synthesis in mouse CFs possibly by downregulating the TGFβ/Smad3 signaling pathway.

Key words: semagutide; cardiac fibroblasts; proliferation