Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells

• Type of Material: Article
• Authors: Desmond B. Jay, Emory University; Christopher A. Papaharalambus, Emory University; Bonnie Seidel-Rogol, Emory University; Anna E. Dikalova, Emory University; Bernard P Lassegue, Emory University; Kathy Griendling, Emory University
• Language: English
• Date: 2008-08-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 Elsevier
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.freeradbiomed.2008.04.024
• Title of Journal or Parent Work: Free Radical Biology and Medicine
• ISSN: 0891-5849
• Volume: 45
• Issue: 3
• Start Page: 329
• End Page: 335
• Grant/Funding Information: This work was supported by NIH grant HL074604 to DBJ and HL058863 to KKG.
• Keywords: vascular smooth muscle cells; proliferation; NADPH oxidase; reactive oxygen species; Nox5
• Research Categories: Biology, Cell; Biology, General

Abstract

The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASMC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASMC proliferation.