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Transforming growth factor-β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo

Citation

Peshavariya, HM and Chan, EC and Liu, GS and Jiang, F and Dusting, GJ, Transforming growth factor-β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo, Journal of Cellular and Molecular Medicine, 18, (6) pp. 1172-1183. ISSN 1582-1838 (2014) [Refereed Article]


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Copyright 2014 The Authors. Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0)

DOI: doi:10.1111/jcmm.12263

Abstract

Angiogenesis, the formation of new blood vessels, is a key physiological event in organ development and tissue responses to hypoxia but is also involved in pathophysiologies such as tumour growth and retinopathies. Understanding the molecular mechanisms involved is important to design strategies for therapeutic intervention. One important regulator of angiogenesis is transforming growth factor-β1 (TGF-β1). In addition, reactive oxygen species (ROS) and the ROS-forming NADPH oxidase type 4 (Nox4) have been implicated as additional regulators such as during hypoxia. Here, we show that both processes are indeed mechanistically linked. TGF-β1-stimulated Nox4 expression and ROS formation in endothelial cells. In cells from Nox4-deficient mice, TGF-β1-induced cell proliferation, migration and tube formation were abolished. In vivo, TGF-β1 stimulated growth of blood vessels into sponges implanted subcutaneously, and this angiogenesis was markedly reduced in Nox4 knockout mice. Thus, endothelial cells are regulated by a TGF-β1 signalling pathway involving Nox4-derived ROS to promote angiogenesis. In order to abrogate pathological angiogenesis triggered by a multitude of factors, such as TGF-β1 and hypoxia, Nox4 may thus be an ideal therapeutic target.

Item Details

Item Type:Refereed Article
Keywords:NADPH oxidase, Nox4, angiogenesis, TGF
Research Division:Technology
Research Group:Medical Biotechnology
Research Field:Gene and Molecular Therapy
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
Author:Liu, GS (Dr Guei-Sheung Liu)
ID Code:120774
Year Published:2014
Web of Science® Times Cited:17
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-08-30
Last Modified:2017-11-06
Downloads:13 View Download Statistics

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