Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells
The Korean Journal of Internal Medicine
Patients with liver cirrhosis (LC) have low levels of branched-chain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti-fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs). LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to TGF-β1 and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs.
... ents of BCAAs. Activation of TGF-β signaling pathways in LX-2 cells were observed using real-time quantitative PCR and western blotting. The increased expression of SNAI1 was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and α-SMA at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 MAPK signaling pathways, respectively. BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.