Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells.

ABSTRACT:

Backgrounds and aims

Activation of hepatic stellate cells (HSCs) is a central driver of fibrosis. This study aimed to elucidate the role of the deacetylase sirtuin 6 (Sirt6) in HSC activation and liver fibrosis.

Approach and results

Gain-of-function and loss-of-function models were used to study the function of Sirt6 in HSC activation. Mass spectrometry was used to determine the specific acetylation site. The lecithin retinol acyltransferase-driven cyclization recombination recombinase construct (CreERT2) mouse line was created to generate HSC-specific conditional Sirt6-knockout mice (Sirt6^△HSC ). We found that Sirt6 is most abundantly expressed in HSCs as compared with other liver cell types. The expression of Sirt6 was decreased in activated HSCs and fibrotic li

SUBMITTER: Zhang J 

PROVIDER: S-EPMC8048913 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature