In the present study, we show in a preclinical setting of clinical relevance that inhibition of ACE is one of the therapy for renal fibrosis which is either directly associated with the suppression of pathobiological mechanisms of DPP-4 and restoration of antifibrotic microRNAs or indirectly by AcSDKP-mediated-restoration of anti-fibrotic microRNAs in kidney whereas treatment of ARB is unable to show such protective effects in the mouse model of diabetic kidney disease. The gene discussed is DPP4; the disease is diabetic kidney disease.