Inhibitory effect of Saxagliptin on high glucose-induced overexpression of LncRNA-MALAT1 in endothelial cells / 医学研究生学报

ABSTRACT

Objective Saxagliptin regulates the level of blood glucose by selectively inhibiting high-performance dipeptidyl peptidase 4, but its action mechanism is not yet clear .This study was to investigate the effect of the novel hypoglycemic agent Saxaglip -tin on the expression of long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and its target gene products transforming growth factor-β1 ( TGF-β1 ) in human umbilical vein endothelial cells ( HUVECs) stimulated by high glucose. Methods HUVECs were cultured in with D-glucose (D-GS) at the concentrations of 5.5, 10, 20, and 30 mmol/L and Saxagliptin at 0, 0.01, 0.1, 1, and 10μmol/L.The best concentrations of D-GS and Saxagliptin were determined as 30 mmol/L and 1 μmol/L, respectively.The HUVECs were divided into four groupscontrol (5.5 mmol/L D-GS), Saxagliptin (5.5 mmol/L D-GS+1 μmol/L Saxagliptin ) , high glucose ( 30 mmol/L D-GS ) , and high glucose +Saxagliptin (30 mmol/L D-GS +1μmol/L Saxaglip-tin), all cultured for 24 hours.Then the expressions of MALAT1 and TGF-β1 mRNA in the cells were detected by qRT-PCR, that of the TGF-β1 protein determined by Western blot , and the level of TGF-β1 in the supernatant measured by ELISA . Results The expressions of LncRNA-MALAT1 and TGF-β1 were significantly increased in the high glucose group as compared with the control ( 8.65 ±0.70 vs1.00 ±0.00 and 1.36 ±0.07 vs 1.00 ±0.00, P<0.01) but markedly inhibited in the high glucose +Saxagliptin group in compari-son with the high glucose group (2.17 ±0.24 vs 8.65 ±0.70 and 1.15 ±0.02 vs 1.36 ±0.07, P<0.05). Conclusion High glu-cose can induce the overexpression of LncRNA-MALAT1 and its target gene products TGF-β1 in HUVECs and cause damage to the cells, while Saxagliptin can significantly suppress this effect .