Smad7 dependent expression signature highlights BMP2 and HK2 signaling in HSC transdifferentiation

被引：6

作者：

Denecke, Bernd ^{[2
]}

Wickert, Lucia ^{[3
]}

Liu, Yan ^{[1
]}

Ciuclan, Loredana

Dooley, Steven ^{[1
]}

Meindl-Beinker, Nadja M. ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Med 2, Med Fac Mannheim, D-68167 Mannheim, Germany

[2] Rhein Westfal TH Aachen, Interdisciplinary Ctr Clin Res IZKF Aachen, D-52074 Aachen, Germany

[3] RWTH Univ Hosp, Inst Clin Chem & Pathobiochem, D-52074 Aachen, Germany

来源：

WORLD JOURNAL OF GASTROENTEROLOGY | 2010年 / 16卷 / 41期

关键词：

Transforming growth factor-beta; Smad7; Hepatic stellate cell; Gene regulation; Glucose metabolism; BMP2; HEPATIC STELLATE CELLS; FATTY LIVER-DISEASE; OXIDATIVE STRESS; INTERFERON-GAMMA; BETA RESPONSE; GROWTH; ACTIVATION; FIBROSIS; MEDIATOR; COLLAGEN;

D O I：

10.3748/wjg.v16.i41.5211

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

AIM: To analyse the influence of Smad7, antagonist of transforming growth factor (TGF)-beta canonical signaling pathways on hepatic stellate cell (HSC) transdifferentiation in detail. METHODS: We systematically analysed genes regulated by TGF-beta/Smad7 in activated HSCs by microarray analysis and validated the results using real time polymerase chain reaction and Western blotting analysis. RESULTS: We identified 100 known and unknown targets underlying the regulation of Smad7 expression and delineated 8 gene ontology groups. Hk2, involved in glycolysis, was one of the most downregulated proteins, while BMP2, activator of the Smad1/5/8 pathway, was extremely upregulated by Smad7. However, BMP2 dependent Smad1 activation could be inhibited in vitro by Smad7 overexpression in HSCs. CONCLUSION: We conclude (1) the existence of a tight crosstalk of TGF-beta and BMP2 pathways in HSCs and (2) a Smad7 dependently decreased sugar metabolism ameliorates HSC activation probably by energy withdrawal. (C) 2010 Baishideng. All rights reserved.

引用

页码：5211 / 5224

页数：14

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