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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background/Aims: 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). Methods: LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real-time quantitative polymerase chain reaction and Western blotting. Results: The increased expression of snail family transcriptional repressor 1 (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 alpha smooth muscle actin 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 mitogen-activated protein kinase signaling pathways, respectively. Conclusions: 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.

Original languageEnglish
Pages (from-to)53-62
Number of pages10
JournalKorean Journal of Internal Medicine
Volume37
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This study was supported by research grants from Hanmi Pharmaceutical Co., Ltd.

Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C1050).

Publisher Copyright:
© 2022 The Korean Association of Internal Medicine.

Keywords

  • Branched-chain amino acids
  • Fibrosis
  • Hepatic stellate cells

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