Notably, in a model of liver fibrosis induced by CCl4 treatment, specific deletion of Sirt2 in hepatocyte also displayed a more evident accumulation of collagen protein, high phosphorylation of SMAD2 and SMAD3, and higher expression of fibrotic genes, such as Serpine1, Col1a1, Col1a2, and Smad7, compared to that in the control liver (Fig. S10, a–d, column 4 vs 3), suggesting that SIRT2 in hepatocytes plays an important role during fibrogenesis not only in the kidney but also in liver tissue. Here, SMAD2 is linked to Hepatic fibrosis.