Fibrotic response induced by angiotensin-II requires NAD(P)H oxidase-induced reactive oxygen species (ROS) in skeletal muscle cells
Date
2011
Type:
Artículo
item.page.extent
item.page.accessRights
item.contributor.advisor
ORCID:
Journal Title
Journal ISSN
Volume Title
Publisher
item.page.isbn
item.page.issn
item.page.issne
item.page.doiurl
item.page.other
item.page.references
Abstract
Fibrotic disorders are typified by excessive connective tissue and extracellular matrix (ECM) deposition that precludes normal healing processes in different tissues. Angiotensin-II (Ang-II) is involved in the fibrotic response. Several muscular dystrophies are characterized by extensive fibrosis. However, the exact role of Ang-II in skeletal muscle fibrosis is unknown. Here we show that myoblasts responded to Ang-II by increasing protein levels of connective tissue growth factor (CTGF/CCN2), collagen-III and fibronectin. These Ang-II-induced pro-fibrotic effects were mediated by AT-1 receptors. Remarkably, Ang-II induced reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism, as shown by inhibition of ROS production via the NAD(P)H oxidase inhibitors diphenylene iodonium (DPI) and apocynin. This increase in ROS is critical for Ang-II-induced fibrotic effects, as indicated by the decrease in Ang-II-induced CTGF and fibronectin levels by DPI and apocynin. We also show that Ang-II-induced ROS production and fibrosis require PKC activity as indicated by the generic PKC inhibitor chelerythrine.
These results strongly suggest that the fibrotic response induced by Ang-II is mediated by AT-I receptor and requires NAD(P)H-induced ROS in skeletal muscle cells. (C) 2011 Elsevier Inc. All rights reserved.
Description
item.page.coverage.spatial
item.page.sponsorship
Citation
Biochemical and Biophysical Research Communications, 2011, vol. 410, n° 3, p. 665-670
Keywords
Angiotensin-II, Fibrosis, NAD(P)H oxidase, Skeletal muscle, Reactive oxygen species (ROS), AT-1 receptor