OBJECTIVETo investigate the effect of fosinopril (Fos) on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II (AngII) -induced down-expression of klotho gene.

METHODSCulture cells, NRK-52E, were incubated with media either AngII or Fos or both of all. Experimental groups incubated with Fos (10(-5) mol/L) were divided according to variant points of time for 0 (control), 3, 6, 12, 24 h. Different concentration of Fos was selected to incubated with culture cells for 0 (control), 10(-9) 10(-8), 10(-7), 10(-6), 10(-5) mol/L at the optimal time point (24 h). Five groups, which were A: control; B: AngII (10(-7) mol/L); C: Fos(10(-5) mol/L); D: AngII (10(-7) mol/L) + Fos(10(-5) mol/L) and E: Cells pretreated with Fos(10(-5) mol/L)12 h incubated with AngII (10(-7) mol/L) were divided to observe the effect of Fos on expression of klotho induced by AngII. RT-PCR and immunohistochemistry (IHC) were applied to evaluate the klotho mRNA and protein expression, respectively.

RESULTSFos up-regulated klotho mRNA in time-dependent manner, and independent of dose-dependent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control (P < 0.05), the down-regulating effect was reversed by incubating both with AngII and Fos (P < 0.05), and Fos could inhibit the down-regulated expression of klotho gene induced by Ang II in NRK-52E.

CONCLUSIONFosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.