| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1930552 | Biochemical and Biophysical Research Communications | 2011 | 6 Pages |
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-1 receptor and requires NAD(P)H-induced ROS in skeletal muscle cells.
► Ang-II increased protein levels of connective tissue growth factor (CTGF/CCN2), collagen-III and fibronectin in C2C12 myoblasts. ► Ang-II-induced pro-fibrotic effects are mediated by AT-1 receptors in C2C12 cells. ► Ang-II induced reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism in C2C12 myoblasts. ► Ang-II-induced ROS is critical for Ang-II-induced fibrotic effects in C2C12 myoblasts. ► Ang-II-induced ROS production and fibrosis require PKC activity in C2C12 cells.
