Transforming growth factor-β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo.
Bottom Line: 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.
Affiliation: Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, East Melbourne, Victoria, Australia; O'Brien Institute, Fitzroy, Victoria, Australia.Show MeSH
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Mentions: Disruption of the intact layer of endothelial cells by using a scratch assay model causes migration and proliferation of adjacent cells to fill in the wounded areas. As expected, TGF-β1 accelerated the wound closure in Adv-GFP infected HUVEC and HMECs (Fig.6A–C). Importantly, TGF-β1-induced wound recovery was abolished by Adv-Nox4i (Fig.6A–C). Similarly, TGF-β1 increased the wound closure in wild-type MHEC when compared with untreated endothelial cells (Fig.6D and E), and this wound recovery response was decreased in Nox4 KO-derived mouse MHEC (Fig.6D and E). These data suggest that TGF-β1 promoted migration and wound closure responses of endothelial cells depend on Nox4.
Affiliation: Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, East Melbourne, Victoria, Australia; O'Brien Institute, Fitzroy, Victoria, Australia.