The above findings suggest that aerobic exercise alleviates renal fibrosis by inhibiting the upstream pathway of Klotho, TGFβ1/p53/miR-34a, upregulating Klotho expression, followed by the inhibition of the activation of its downstream pathways, Wnt/β-catenin/MMP7 and TGFβ1/Smad3, thereby ameliorating renal fibrosis. This evidence concerns the gene SMAD3 and renal fibrosis.