TY - JOUR
T1 - Reactive oxygen species production via NADPH oxidase mediates TGF-β-induced cytoskeletal alterations in endothelial cells
AU - Hu, Taishan
AU - RamachandraRao, Satish P.
AU - Siva, Senthuran
AU - Valancius, Cathryn
AU - Zhu, Yanqing
AU - Mahadev, Kalyankar
AU - Toh, Irene
AU - Goldstein, Barry J.
AU - Woolkalis, Marilyn
AU - Sharma, Kumar
PY - 2005/10
Y1 - 2005/10
N2 - Cytoskeletal alterations in endothelial cells have been linked to nitric oxide generation and cell-cell interactions. Transforming growth factor (TGF)-β 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-β treatment resulting in filipodia formation and F-actin assembly. The cytoskeletal alterations were blocked by the novel TGF-β type I receptor/ALK5 kinase inhibitor (SB-505124) but not by the p38 kinase inhibitor (SB-203580). TGF-β also induced marked stimulation of reactive oxygen species (ROS) within 5 min of TGF-β exposure. TGF-β 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-β effect on cytoskeleton changes in endothelial cells. In conclusion, our studies show for the first time that TGF-β-induced ROS production in human endothelial cells is via Nox4 and that TGF-β alteration of cytoskeleton in HUVEC is mediated via a Nox4-dependent pathway.
AB - Cytoskeletal alterations in endothelial cells have been linked to nitric oxide generation and cell-cell interactions. Transforming growth factor (TGF)-β 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-β treatment resulting in filipodia formation and F-actin assembly. The cytoskeletal alterations were blocked by the novel TGF-β type I receptor/ALK5 kinase inhibitor (SB-505124) but not by the p38 kinase inhibitor (SB-203580). TGF-β also induced marked stimulation of reactive oxygen species (ROS) within 5 min of TGF-β exposure. TGF-β 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-β effect on cytoskeleton changes in endothelial cells. In conclusion, our studies show for the first time that TGF-β-induced ROS production in human endothelial cells is via Nox4 and that TGF-β alteration of cytoskeleton in HUVEC is mediated via a Nox4-dependent pathway.
KW - Cell-cell interactions
KW - Cytoskeletal rearrangement
KW - Human umbilical vein endothelial cells
KW - Transforming growth factor-β
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U2 - 10.1152/ajprenal.00024.2005
DO - 10.1152/ajprenal.00024.2005
M3 - Article
C2 - 16159901
AN - SCOPUS:24944557079
VL - 289
SP - F816-F825
JO - American journal of physiology. Renal physiology
JF - American journal of physiology. Renal physiology
SN - 0363-6127
IS - 4 58-4
ER -