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Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Journal of Korean Medical Science 2021년 36권 14호 p.90 ~ 90
박지원, 김모종, 김성은, Kim Hee-Jun, 전용철, 신해영, 박세진, 장명국, 김동준, 박충기, 최은경,
소속 상세정보
박지원 ( Park Ji-Won ) - Hallym University Medical Center Department of Internal Medicine
김모종 ( Kim Mo-Jong ) - Hallym University Graduate School Department of Biomedical Gerontology
김성은 ( Kim Sung-Eun ) - Hallym University Medical Center Department of Internal Medicine
 ( Kim Hee-Jun ) - Hallym University Ilsong Institute of Life Science
전용철 ( Jeon Yong-Chul ) - Hallym University Ilsong Institute of Life Science
신해영 ( Shin Hae-Young ) - Hallym University Ilsong Institute of Life Science
박세진 ( Park Se-Jin ) - Hallym University Ilsong Institute of Life Science
장명국 ( Jang Myoung-Kuk ) - Hallym University Kangdong Sacred Heart Hospital Department of Internal Medicine
김동준 ( Kim Dong-Joon ) - Hallym University Chuncheon Sacred Heart Hospital Department of Internal Medicine
박충기 ( Park Choong-Kee ) - Hallym University Medical Center Department of Internal Medicine
최은경 ( Choi Eun-Kyoung ) - Hallym University Graduate School Department of Biomedical Gerontology

Abstract


Background: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL).

Methods: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis.

Results: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B.

Conclusion: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

키워드

S100B; Receptor for Advanced Glycation End Products; Liver Fibrosis; Bile Duct Ligation

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