The results showed that Klotho knockdown aggravated basal and UUO-induced kidney injury and renal fibrosis (from basal fibrosis of 4% to approximate 18%, and 26% to 43% after UUO, respectively, Fig. 6A,B) and exacerbated the expression of E-cadherin, α-SMA, β-catenin, and phosphorylated Smad3 (Fig. 6C,D, comparing lane 1/2 to 7/8). This evidence concerns the gene SMAD3 and fibrosis.