NAD(P)H oxidase-derived reactive oxygen species regulate angiotensin-II induced adventitial fibroblast phenotypic differentiation

作者：Shen, WL; Gao, PJ^*; Che, ZQ; Ji, KD; Yin, M; Yan, C; Berk, BC; Zhu, DL

来源：Biochemical and Biophysical Research Communications, 2006, 339(1): 337-343.

DOI：10.1016/j.bbrc.2005.10.207

• reactive oxygen species
• adventitial fibroblast
• differentiation

Phenotypic differentiation of adventitial fibroblasts is an essential feature of vascular remodeling. The present study was undertaken to test the hypothesis that reactive oxygen species (ROS) are involved in rate adventitial fibroblast differentiation to myofibroblast. Activation of alpha-smooth muscle a'ctin (alpha-SMA) was used as a marker of myofibroblast. Angiotensin II increased intracellular ROS in adventitial fibroblasts that was completely inhibited be 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, 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 pathway.

• 出版日期2006-1-6
• 单位上海市闵行区中心医院; 上海交通大学