Abrogation of transforming growth factor-β-induced tissue fibrosis in mice with a global genetic deletion of Nox4.

ABSTRACT: Excessive connective tissue deposition in skin and various internal organs is characteristic of systemic sclerosis (SSc). The profibrotic growth factor TGF-β plays a crucial role in SSc pathogenesis. The expression of NADPH oxidase 4 (NOX4), a critical mediator of oxidative stress, is potently stimulated by TGF-β. Here, we evaluated the effect of NOX4 on the development of TGF-β-induced tissue fibrosis. C57BL6/J control mice and Nox4 knockout mice were implanted subcutaneously with osmotic pumps containing either saline or 2.5 µg TGF-β1. After 28 days, skin and lung samples were isolated for histopathologic analysis, measurement of hydroxyproline content and gene expression analysis. Histopathology of skin and lungs from normal C57BL6/J mice treated with TGF-β1 showed profound dermal fibro

SUBMITTER: Wermuth PJ 

PROVIDER: S-EPMC6530913 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature