TGFB1 and Hepatic fibrosis: Sirt6 alleviated phosphorylated mothers against decapentaplegic homolog (Smad) 2 levels as well as its nuclear transcription to suppress liver fibrosis in hepatic stellate cells, and in Sirt6 whole-body knockout mice, the up-regulation of TGFβ contributed to collagen deposition and ECM remodeling to facilitate cardiac, hepatic, renal and pulmonary fibrosis (Xiao et al. 2012; Maity et al. 2020).