Hypertrophic response to angiotensin II is mediated by protein kinase D-extracellular signal-regulated kinase 5 pathway in human aortic smooth muscle cells.
Angiotensin II plays a critical role in hypertrophy of vascular smooth muscle cells, however, the molecular underpinnings remain unclear. The present study indicated that AT1/PKC/PKD pathway was able to regulate downstream ERK5, affecting pro-hypertrophic responses to Ang II. Ang II-stimulated phosphorylation of ERK5 in a time- and dose-dependent manner in human aortic smooth muscle cells (HASMCs). The pharmacological inhibitors for AT1 and PKCs significantly inhibited Ang II-induced ERK5 activation, suggesting the involvement of the AT1/PKC pathway. In particular, PKD was critical for Ang II-induced ERK5 activation since silencing PKD by siRNA markedly inhibited Ang II-induced ERK5 activation. Consequently, we found that Losartan, Gö 6983 and PKD siRNA significantly attenuated ERK5 activated translocation and hypertrophy of HASMCs by Ang II. Taken together, we demonstrated for the first time that Ang II activates ERK5 via the AT1/PKC/PKD pathway and revealed a critical role of ERK5 in Ang II-induced HASMCs hypertrophy.
Geng
Jing
J
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, PR China.
Zhao
Zhuo
Z
Kang
Weiqiang
W
Wang
Wei
W
Liu
Guanghui
G
Sun
Yingying
Y
Zhang
Yun
Y
Ge
Zhiming
Z
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology*; D055785:Gene Knockdown Techniques; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction
D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C089212:protein kinase D; D011493:Protein Kinase C; D048054:Mitogen-Activated Protein Kinase 7