NAD(P)H oxidase-derived reactive oxygen species regulate angiotensin-II induced adventitial fibroblast phenotypic differentiation
| Autor: | Dingliang Zhu, Weili Shen, Kaida Ji, Ming Yin, Chen Yan, Pingjin Gao, Zai-Qian Che, Bradford C. Berk |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Pyridines p38 mitogen-activated protein kinases Biophysics Aorta Thoracic p38 Mitogen-Activated Protein Kinases Biochemistry Losartan Oligodeoxyribonucleotides Antisense Rats Sprague-Dawley medicine Animals Phosphorylation Molecular Biology Cells Cultured Anthracenes Membrane Glycoproteins Angiotensin II receptor type 1 NADPH oxidase biology Angiotensin II Imidazoles JNK Mitogen-Activated Protein Kinases NADPH Oxidases Cell Differentiation Free Radical Scavengers Cell Biology Fibroblasts Free radical scavenger Molecular biology Rats Connective Tissue NAD(P)H oxidase NADPH Oxidase 2 biology.protein Reactive Oxygen Species Angiotensin II Type 1 Receptor Blockers Myofibroblast medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 339:337-343 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.10.207 |
| Popis: | Phenotypic differentiation of adventitial fibroblasts into myofibroblasts is an essential feature of vascular remodeling. The present study was undertaken to test the hypothesis that reactive oxygen species (ROS) are involved in rat adventitial fibroblast differentiation to myofibroblast. Activation of alpha-smooth muscle actin (alpha-SMA) was used as a marker of myofibroblast. Angiotensin II increased intracellular ROS in adventitial fibroblasts that was completely inhibited by the free radical scavenger NAC, the NAD(P)H oxidase inhibitor DPI, and transfection of antisense gp91phox oligonucleotides. Myofibroblast differentiation was prevented by inhibition of ROS generation with DPI, NAC, and antisense gp91phox as shown by decreased expression of alpha-SMA. Angiotensin II rapidly induced phosphorylation of p38 MAPK and JNK, both of which were inhibited by DPI, NAC, antisense gp91phox, and the selective AT1 receptor antagonist, losartan. Inhibiting p38MAPK with SB202190 or JNK with SP600125 also reduced angiotensin II-induced alpha-SMA expression. These findings demonstrate that angiotensin II induces adventitial fibroblast differentiation to myofibroblast via a pathway that involves NADPH oxidase generation of ROS and activation of p38MAPK and JNK pathways. |
| Databáze: | OpenAIRE |
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