한빛사논문
- 조회2,626
Abstract
Chang Yeob Han1, Ja Hyun Koo1, Sung Hoon Kim2, Sara Gardenghi3, Stefano Rivella3, Pavel Strnad4, Se Jin Hwang2 & Sang Geon Kim1,*
1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea. 2 College of Medicine, Hanyang University, Seoul 04763, Korea. 3 Department of Pediatrics, Division of Hematology-Oncology, Weill Cornell Medical College, New York, New York 10021, USA. 4 IZKF and Department of Internal Medicine III, University Hospital Aachen, Aachen 52074, Germany.
*Correspondence to Sang Geon Kim.
Abstract
Hepatic stellate cell (HSC) activation on liver injury facilitates fibrosis. Hepatokines affecting HSCs are largely unknown. Here we show that hepcidin inhibits HSC activation and ameliorates liver fibrosis. We observe that hepcidin levels are inversely correlated with exacerbation of fibrosis in patients, and also confirm the relationship in animal models. Adenoviral delivery of hepcidin to mice attenuates liver fibrosis induced by CCl4 treatment or bile duct ligation. In cell-based assays, either hepcidin from hepatocytes or exogenous hepcidin suppresses HSC activation by inhibiting TGFβ1-mediated Smad3 phosphorylation via Akt. In activated HSCs, ferroportin is upregulated, which can be prevented by hepcidin treatment. Similarly, ferroportin knockdown in HSCs prohibits TGFβ1-inducible Smad3 phosphorylation and increases Akt phosphorylation, whereas ferroportin over-expression has the opposite effect. HSC-specific ferroportin deletion also ameliorates liver fibrosis. In summary, hepcidin suppresses liver fibrosis by impeding TGFβ1-induced Smad3 phosphorylation in HSCs, which depends on Akt activated by a deficiency of ferroportin.
논문정보
- Research article
- 2016년 12월 (BRIC 등록일 2016-12-27)
- 국내(교신)+국외 연구진
- 의약학 > 약학
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