Abstract: Objective To investigate the effect of anagliptin on fibrosis of myocardial fibroblasts(MCFs) induced by high glucose and its mechanism of action. 
Methods MCFs were treated with 5.50 and 25.00 mmol/L glucose respectively and divided into low glucose group and high glucose group. Anagliptin(0.05, 0.10, 0.20 μmol/L) was used for the treatment of MCFs induced by high glucose for 6 h, and the optimal concentration screened was 0.10 μmol/L. The mimics-NC group(transfected mimics-NC), miR-497-5p group(transfected miR-497-5p), anti-NC group(transfected anti-NC), anti-miR-497-5p group(transfected anti-miR-497-5p), si-NC group(transfected si-NC), si-glycosylphosphatidylinositol specific phospholipase D1(GPLD1) group(transfected si-GPLD1), anagliptin + mimics-NC group(transfected mimics-NC), anagliptin+miR-497-5p group(transfected miR-497-5p), anagliptin + mir-497-5p + pcDNA group(co-transfected miR-497-5p and pcDNA), anagliptin + miR-497-5p + pcDNA-GPLD1 group(co-transfected miR-497-5p and pcDNA-GPLD1) were transfected into MCFs and treated with 25.00 mmol/L glucose or 0.10 μmol/L anagliptin. Western blotting(WB) assay, and real time fluorescence quantitative polymerase chain reaction(RT-qPCR) were used to detect the protein expression of alpha smooth muscle actin(α-SMΑ), collagen Ⅰ(Col Ⅰ), collagen Ⅲ(Col Ⅲ) and the expression of miR-497-5p and GPLD1 in cells of each group. Double luciferase reporter gene assay was used to detect the fluorescence activity of cells. 
Results Compared with NG group, the protein expression of α-SMA, Col Ⅰ and Col Ⅲ increased significantly, while miR-497-5p decreased significantly in HG group(P＜0.05). Anagliptin(0.10, 0.20 μmol/L) significantly inhibited the increase in α-SMA, Col Ⅰ and Col Ⅲ protein and the decrease in mir-497-5p in high glucose-induced MCFs in a concentration-dependent manner. After overexpression of miR-497-5p, the expression of α-SMA, Col Ⅰ and Col Ⅲ proteins decreased significantly in high glucose-induced MCFs. miR-497-5p inhibited the fluorescence activity of wild-type GPLD1 cells and negatively regulated the protein expression of GPLD1. Knockdown of GPLD1 inhibited high glucose-induced effect of α-SMA, Col Ⅰ and Col Ⅲ protein expression in MCFs, similar to overexpression of miR-497-5p. Overexpression of GPLD1 could significantly weaken the effect of anagliptin and overexpression of miR-497-5p on inhibition of α-SMA, Col Ⅰ and Col Ⅲ expression in high glucose-induced MCFs. 
Conclusion Anagliptin could inhibit the fibrosis of MCFs induced by high glucose, and its mechanism may be related to the regulation of miR-497-5p/GPLD1 signaling pathway. 

Key words: diabetic cardiomyopathy, anagliptin, fibrosis