NOX in liver fibrosis

被引：136

作者：

De Minicis, Sarnuele ^{[1
]}

Brenner, David A. ^{[1
]}

机构：

[1] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10026 USA

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2007年 / 462卷 / 02期

关键词：

liver fibrosis; hepatic stellate cells; NADPH oxidase (NOX); reactive oxygen species (ROS); angiotensin II; PDGF; apoptotic bodies; p47(phox) component; Rac1; component;

D O I：

10.1016/j.abb.2007.04.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

NADPH oxidase is a multi-protein complex producing reactive oxygen species (ROS) both in phagocytic cells, being essential in host defense, and in non-phagocytic cells, regulating intracellular signalling. In the liver, NADPH oxidase plays a central role in fibrogenesis. A functionally active form of the NADPH oxidase is expressed not only in Kupffer cells (phagocytic cell type) but also in hepatic stellate cells (HSCs) (non-phagocytic cell type), suggesting a role of the non-phagocytic NADPH oxidase in HSC activation. Consistent with this concept, profibrogenic agonists such as Angiotensin 11 (Ang 11) and platelet derived growth factor (PDGF), or apoptotic bodies exert their activity through NADPH oxidase-activation in HSCs. Both pharmacological inhibition with DPI and genetic studies using p47(phox) knockout mice provided evidence for a central role of NADPH oxidase in the regulation of HSC-activity and liver fibrosis. In addition to the p47(phox) component, only Racl has been identified as a functional active component of the NADPH oxidase complex in HSCs. Published by Elsevier Inc.

引用

页码：266 / 272

页数：7

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