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. This evidence concerns the gene TMSB4X and renal fibrosis.