ATF3-mediated transactivation of CXCL14 in HSCs during liver fibrosis.

ABSTRACT:

Background and aims

Myofibroblasts, the primary producers of extracellular matrix, primarily originate from hepatic stellate cells (HSCs), and their activation plays a pivotal role in liver fibrosis. This study aimed to investigate the function of CXC motif ligand 14 (CXCL14) in the progression of liver fibrosis.

Approach and results

CXCL14 knockdown significantly reduced the extent of liver fibrosis. Using Ingenuity pathway analysis and qRT-PCR, activating transcription factor 3 (ATF3) was identified as a key upstream regulator of CXCL14 expression. Mechanistically, ATF3 was shown to bind to the CXCL14 promoter, promoting its transactivation by TGF-β in HSCs. Notably, both global CXCL14 deletion (CXCL14^-/-) and HSC/myofibroblast-specific CXCL14 knockdown signific

SUBMITTER: Li X 

PROVIDER: S-EPMC11446984 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature