Effect of DPP4 inhibitor sitagliptin on expressions of early growth response-1 and fibronectin in the kidney of ApoE gene knockout mice / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice.</p><p><b>METHODS</b>Eight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and Western blotting.</p><p><b>RESULTS</b>The mice in both apoE(-/-) group and sitagliptin+apoE(-/-) group all showed prominently increased blood lipids as compared with the control group (P<0.05) without significant differences between the two apoE(-/-) groups. The level of HDL was significantly higher in sitagliptin +apoE(-/-) group than in apoE(-/-) group (P<0.001) and control group (P<0.001). IPGTT showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was increased in apoE(-/-) group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE(-/-) group than in apoE(-/-) group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein expressions of renal cortical Egr-1 and fibronectin in sitagliptin+apoE(-/-) group compared with apoE(-/-) group.</p><p><b>CONCLUSION</b>Sitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection.</p>