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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 Statement
Copyright 2014 The Authors. Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0)
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 |
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Keywords: | NADPH oxidase, Nox4, angiogenesis, TGF |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Medical biotechnology |
Research Field: | Gene and molecular therapy |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Liu, GS (Associate Professor Guei-Sheung Liu) |
ID Code: | 120774 |
Year Published: | 2014 |
Web of Science® Times Cited: | 36 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2017-08-30 |
Last Modified: | 2017-11-06 |
Downloads: | 116 View Download Statistics |
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