MilliporeSigma

Myofibroblast-specific YY1 promotes liver fibrosis.

Biochemical and biophysical research communications (2019-05-16)
Huan Liu, Shuya Zhang, Suowen Xu, Marina Koroleva, Eric M Small, Zheng Gen Jin
ABSTRACT

Liver fibrosis is a common consequence of various chronic hepatitis and liver injuries. The myofibroblasts, through the accumulation of extracellular matrix (ECM) proteins, are closely associated with the progression of liver fibrosis. However, the molecular mechanisms underlying transcriptional regulation of fibrogenic genes and ECM proteins in myofibroblasts remain largely unknown. Using tamoxifen inducible myofibroblast-specific Cre-expressing mouse lines with selective deletion of the transcription factor Yin Yang 1 (YY1), here we show that YY1 deletion in myofibroblasts mitigates carbon tetrachloride-induced liver fibrosis. This protective effect of YY1 ablation on liver fibrosis was accompanied with reduced expression of profibrogenic genes and ECM proteins, including TNF-α, TGF-β, PDGF, IL-6, α-SMA and Col1α1 in liver tissues from YY1 mutant mice. Moreover, using the human hepatic stellate cell (HSC) line LX-2, we found that knockdown of YY1 in myofibroblasts by siRNA treatment diminished myofibroblast proliferation, α-SMA expression, and collagen deposition. Collectively, our findings reveal a specific role of YY1 in hepatic myofibroblasts and suggest a new therapeutic strategy for hepatic fibrosis-associated liver diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
EmbryoMax® L-Glutamine Solution (100X), 200mM, The EmbryoMax L-Glutamine Solution (100X), 200mM is available in a 100 mL format and may be used for routine mouse embryonic stem cell culture applications.
Sigma-Aldrich
LX-2 Human Hepatic Stellate Cell Line, The LX-2 human hepatic stellate cell line has been extensively characterized and retain key features of hepatic stellate cytokine signaling, neuronal gene expression, retinoid metabolism, and fibrogenesis, making them a highly suitable model of human hepatic fibrosis.