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Irisin Regulates the Functions of Hepatic Stellate Cells

Endocrinology and Metabolism 2020년 35권 3호 p.647 ~ 655
Dong Hanh Nguyen, 박소영, Le Cong Thuc, 최대희, 조은희,
소속 상세정보
 ( Dong Hanh Nguyen ) - Kangwon National University School of Medicine Department of Internal Medicine
박소영 ( Park So-Young ) - Kangwon National University School of Medicine Department of Internal Medicine
 ( Le Cong Thuc ) - Kangwon National University School of Medicine Department of Internal Medicine
최대희 ( Choi Dae-Hee ) - Kangwon National University School of Medicine Department of Internal Medicine
조은희 ( Cho Eun-Hee ) - Kangwon National University School of Medicine Department of Internal Medicine

Abstract


Background: Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs are activated, they are involved in proliferation, migration, and contractility which are characteristics of liver fibrogenesis. Recent studies have shown that irisin, a myokine secreted during physical exercise, has a protective effect in various metabolic diseases, especially in renal fibrosis. However, whether irisin is involved in HSC activation and other processes associated with liver fibrosis has not yet been investigated. In this study, we reveal the role of irisin in HSC activation as well as in proliferation, migration, and contractile properties of HSCs in vitro.

Methods: LX-2 cells, immortalized human HSCs, were treated with transforming growth factor beta 1 (TGF-β1), a core regulator of HSC fibrosis, with or without irisin, and markers of the aforementioned processes were analyzed. Further, an inflammatory response was stimulated with TGF-β1 and lipopolysaccharide (LPS) in combination with irisin and the expression of cytokines was measured.

Results: Recombinant irisin significantly suppressed the expression of TGF-β1-stimulated fibrosis markers including alpha-smooth muscle actin and collagen type 1 alpha 1 and prevented the TGF-β1-induced proliferation, migration, and contractility of LX-2 cells. Additionally, irisin ameliorated the production of interleukin-6 (IL-6) and IL-1β induced by TGF-β1 and LPS treatments.

Conclusion: These findings suggested that irisin potently improved the progression of hepatic fibrosis by regulating HSC activation, proliferation, migration, contractility, and HSC-mediated production of inflammatory cytokine.

키워드

Hepatic stellate cells; Irisin; Lipopolysaccharides; Liver cirrhosis; Transforming growth factor beta1

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