Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells

Hae Lim Lee, Jungmin Lee, Jung Hoon Cha, Sungwoo Cho, Pil Soo Sung, Wonhee Hur, Seung Kew Yoon, Si Hyun Bae
2020 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.
more » ... 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.
doi:10.3904/kjim.2020.197 pmid:32872742 fatcat:nycw2e4dkbhtfjuvdmm4u2eb2q