Anti-aging gene Klotho ameliorates diabetic nephropathy in mice by inhibiting FGF2 signaling pathway.

Abstract

The aim of this study was to observe the expression of Klotho in renal tissues of mice with diabetic ne¬phropathy (DN), and to further explore the effect of Klotho on DN in mice and its mechanism. The 10-week-old mice in this experiment were divided into three groups: heterozygous db/+ mouse group (db/+ group, n=20), homozygous db/db mouse group (db/db group, n=20) and homozygous db/db mice + Klotho group (db/db + Klotho group, n=20). Firstly, Western blotting and immunohistochemical staining were applied to detect the protein expression of Klotho in the renal tissues of diabetic and non-diabetic mice of different ages. Finally, the protein expressions of fibroblast growth factor 2 (FGF2) and E-cadherin in the renal tissues of mice in each group were examined by Western blotting. The protein expression level of Klotho in the renal tissues of mice aged 10 and 16 weeks in the db/db group was remarkably lower than that in yhedb/+ group. In addition, it was found that db/db + Klotho group exhibited a prominently lower degree of interstitial fi¬brosis and content of Collagen I and Collagen III in the renal tissues than db/db group. Furthermore, it was revealed that the overexpression of Klotho could significantly repress the protein expression level of FGF2 but elevate that of E-cadherin in the renal tissues of DN mice. Klotho protein may ameliorate the renal injury and fibrosis in diabetic mice by inhibiting FGF2, so it is expected to become a targeted drug for DN.