Xue Zhou
Huazhong University of Science and Technology, China
Title: Sirtuin-6 inhibits epithelial to mesenchymal transition via inactivation TGF-β/smad signaling in vitro and in vivo
Biography
Biography: Xue Zhou
Abstract
Sirtuin6 (SIRT6), a member of NAD+-dependent deacetylases that plays a key role in aging, cancer, and metabolism, has been shown to have anti-fibrosis function in heart and liver, but whether SIRT6 plays a role in idiopathic pulmonary fibrosis (IPF) has been poorly explored. Epithelial to mesenchymal cell transition (EMT), a process by which fully differentiated epithelial cells convert to a mesenchymal phenotype, has been involved in the pathogenesis of IPF. In the present study, SIRT6 expression was upregulated in both TGF-β1-induced EMT in A549 cells and bleomycin (BLM)-induced EMT in mice. Forced expression of SIRT6 by adenovirus transfection of A549 cells significantly abrogated TGF-β1-induced EMT-like phenotype and EMT-associated cell behavior. In A549 cells, TGF-β1-induced activation of TGF-β1/smad3 signaling and increase of smad3-snail1 interaction was ameliorated by overexpression of SIRT6. Upregulation of EMT related transcription factors by TGF-β1 treatment was also restored by overexpression of SIRT6. Further in vivo studies showed that lung targeted delivery of SIRT6 using adeno-associated virus transfection blunted BLM-induced pulmonary EMT and fibrosis as evidenced by a reduction of epithelium undergoing EMT and collagen deposition. Our findings unravel a novel role of SIRT6 as a key modulator in the phenotypic conversion of epithelial to mesenchymal cells and suggest it as an attractive potential therapeutic target for IPF.