Role of the JAK2/STAT3 pathway in angiotensin II-induced enhanced expression of Giα proteins and hyperproliferation of aortic vascular smooth muscle cells.
We earlier showed that angiotensin (Ang) II-induced overexpression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells (VSMC). In addition, the implication of the JAK2/STAT3 pathway in Ang II-induced hyperproliferation of VSMC has also been reported. However, the role of the JAK2/STAT3 pathway in Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC remains unexplored. In the present study, we show that inhibition or knockdown of the JAK2/STAT3 pathway by a specific inhibitor "cucurbitacin I" (CuI) or siRNAs attenuated Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC. In addition, the enhanced expression of cell cycle proteins induced by Ang II was also attenuated by CuI. Furthermore, Ang II-induced enhanced production of the superoxide anion (O2 -), H2O2, and NADPH oxidase activity, as well as the enhanced expression of NADPH oxidase subunits implicated in enhanced expression of Giα proteins and hyperproliferation, were also attenuated by inhibition of the JAK2/STAT3 pathway. On the other hand, Ang II-induced inhibition and augmentation of the levels of nitric oxide and peroxynitrite, respectively, in VSMC were restored to control levels by CuI. In summary, our results demonstrate that Ang II through the JAK2/STAT3 pathway increases nitroxidative stress, which contributes to the overexpression of Giα proteins and cell cycle proteins and the hyperproliferation of VSMC.
['Hossain|Ekhtear|E|', 'Li|Yuan|Y|', 'Anand-Srivastava|Madhu B|MB|']
D000804:Angiotensin II D000818:Animals D001011:Aorta D049109:Cell Proliferation D019206:GTP-Binding Protein alpha Subunits, Gi-Go D005786:Gene Expression Regulation D006861:Hydrogen Peroxide D053614:Janus Kinase 2 D009131:Muscle, Smooth, Vascular D018384:Oxidative Stress D010766:Phosphorylation D051381:Rats D011918:Rats, Inbred SHR D050796:STAT3 Transcription Factor D015398:Signal Transduction
hyperproliferation VSMC JAK/STAT pathway angiotensin II angiotensine II cellules musculaires lisses vasculaires hyperprolifération oxidative stress stress oxydatif voie de signalisation JAK/STAT