Affordable Access

Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells.

Authors
  • Hu, Taishan
  • Ramachandrarao, Satish P
  • Siva, Senthuran
  • Valancius, Cathryn
  • Zhu, Yanqing
  • Mahadev, Kalyankar
  • Toh, Irene
  • Goldstein, Barry J
  • Woolkalis, Marilyn
  • Sharma, Kumar
Type
Published Article
Journal
American Journal of Physiology - Renal Physiology
Publisher
American Physiological Society
Publication Date
Oct 01, 2005
Volume
289
Issue
4
Identifiers
PMID: 16159901
Source
Medline
License
Unknown

Abstract

Cytoskeletal alterations in endothelial cells have been linked to nitric oxide generation and cell-cell interactions. Transforming growth factor (TGF)-beta has been described to affect cytoskeletal rearrangement in numerous cell types; however, the underlying pathway is unclear. In the present study, we found that human umbilical vein endothelial cells (HUVEC) have marked cytoskeletal alterations with short-term TGF-beta treatment resulting in filipodia formation and F-actin assembly. The cytoskeletal alterations were blocked by the novel TGF-beta type I receptor/ALK5 kinase inhibitor (SB-505124) but not by the p38 kinase inhibitor (SB-203580). TGF-beta also induced marked stimulation of reactive oxygen species (ROS) within 5 min of TGF-beta exposure. TGF-beta stimulation of ROS was mediated by the NAPDH oxidase homolog Nox4 as DPI, an inhibitor of NADPH oxidase, and dominant-negative Nox4 adenovirus blocked ROS production. Finally, inhibition of ROS with ROS scavengers or dominant-negative Nox4 blocked the TGF-beta effect on cytoskeleton changes in endothelial cells. In conclusion, our studies show for the first time that TGF-beta-induced ROS production in human endothelial cells is via Nox4 and that TGF-beta alteration of cytoskeleton in HUVEC is mediated via a Nox4-dependent pathway.

Report this publication

Statistics

Seen <100 times