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Fibrotic response induced by angiotensin-II requires NAD(P)H oxidase-induced reactive oxygen species (ROS) in skeletal muscle cells

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dc.contributor.author Cabello-Verrugio, Claudio
dc.contributor.author Acuña, Maria José
dc.contributor.author Morales, Maria Gabriela
dc.contributor.author Becerra, Alvaro
dc.contributor.author Simon, Felipe
dc.contributor.author Brandan, Enrique
dc.date.accessioned 2016-12-15T15:26:14Z
dc.date.available 2016-12-15T15:26:14Z
dc.date.issued 2011
dc.identifier.citation Biochemical and Biophysical Research Communications, 2011, vol. 410, n° 3, p. 665-670
dc.identifier.uri http://hdl.handle.net/11447/897
dc.identifier.uri http://dx.doi.org/10.1016/j.bbrc.2011.06.051
dc.description.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.
dc.language.iso en_US
dc.subject Angiotensin-II
dc.subject Fibrosis
dc.subject NAD(P)H oxidase
dc.subject Skeletal muscle
dc.subject Reactive oxygen species (ROS)
dc.subject AT-1 receptor
dc.title Fibrotic response induced by angiotensin-II requires NAD(P)H oxidase-induced reactive oxygen species (ROS) in skeletal muscle cells
dc.type Artículo


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