Sirtuin 6 inhibits myofibroblast differentiation via inactivating transforming growth factor-β1/Smad2 and nuclear factor-κB signaling pathways in human fetal lung fibroblasts

Journal of Cellular Biochemistry
Qian ZhangXue Zhou

Abstract

Fibroblast-to-myofibroblast differentiation, which is characterized by increased expression of α-smooth muscle actin, is known to be involved in the pathogenesis of idiopathic pulmonary fibrosis. Sirtuin 6 (SIRT6), a member of the sirtuin family, has been proved to inhibit epithelial-to-mesenchymal transition during idiopathic pulmonary fibrosis. However, the function of SIRT6 in lung myofibroblast differentiation is still obscure. Transforming growth factor-β1 (TGF-β1) is one of the main factors that can powerfully promote myofibroblast differentiation. In the current study, we aimed to explore the role of SIRT6 in the cellular model of fibroblast-to-myofibroblast differentiation induced by TGF-β1 using human fetal lung fibroblasts (HFL1). We demonstrated that the SIRT6 protein level is upregulated by TGF-β1 in HFL1 cells. Overexpression of SIRT6 significantly suppresses TGF-β1-induced myofibroblast differentiation in HFL1 cells. Mechanistically, SIRT6 decreases phosphorylation and nuclear translocation of Smad2 under TGF-β1 stimulation. Nevertheless, mutant SIRT6 (H133Y) without histone deacetylase activity fails to inhibit phosphorylation and nuclear translocation of Smad2. Meanwhile, SIRT6 interacts with the nuclear factor-...Continue Reading

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Citations

Apr 17, 2019·Molecular and Cellular Biochemistry·Xueyi WuLizhi Wang
Apr 3, 2019·Bone Research·Kayley M UsherJiake Xu
Jun 15, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jinhang ZhangJinhan He
Oct 3, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xie SaiyangTang Qizhu
Dec 15, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sushweta MahalanobishParames C Sil
Nov 25, 2020·International Journal of Molecular Sciences·Przemysław KapustaMichał T Seweryn
Aug 12, 2020·Life Sciences·Somnath MazumderSamik Bindu
Apr 16, 2021·Frontiers in Cell and Developmental Biology·Xiaokang LiHaiyan Wang
Jun 3, 2021·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Alberto ZulloWerner Klingler
Jul 28, 2021·European Journal of Medicinal Chemistry·Lin YueTinghong Ye

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