Besides, it has also been illustrated that with the activation of AMPK, metformin (10 mM) reduces transforming growth factor beta (TGF-β)-induced renal fibroblast collagen type I production via inhibiting Smad3-driven connective tissue growth factor (CTGF) expression, and this mechanism may provide a potential role for metformin in the treatment of chronic kidney disease (CKD) through suppressing renal interstitial fibrosis [69]. This evidence concerns the gene SMAD3 and chronic kidney disease.