120774 Journal Article.pdf (1.13 MB)
Transforming growth factor-β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo
journal contribution
posted on 2023-05-19, 10:44 authored by Peshavariya, HM, Chan, EC, Guei-Sheung LiuGuei-Sheung Liu, Jiang, F, Dusting, GJAngiogenesis, 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.
History
Publication title
Journal of Cellular and Molecular MedicineVolume
18Issue
6Pagination
1172-1183ISSN
1582-1838Department/School
Menzies Institute for Medical ResearchPublisher
Carol Davila Univ PressPlace of publication
8 Eroilor Sanitari Blvd, Bucharesst, Romania, 76241Rights statement
Copyright 2014 The Authors. Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0)Repository Status
- Open