Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8361081 | Regulatory Peptides | 2013 | 8 Pages |
Abstract
Putative protective mechanisms of angiotensin-converting enzyme 2 (ACE2) against Ang II-mediated oxidative stress and VSMC proliferation. In this work, a marked elevation in suppressors of cytokine signaling 3 (SOCS3) expression induced by angiotensin II (Ang II) was observed in cultured human umbilical artery smooth muscle cells (HUASMCs), accompanied by significant increases in phosphorylation levels of Janus kinase 2 (JAK2), signal transducer and activators of transcription 3 (STAT3) and extracellular regulated protein kinases 1/2 (ERK1/2), leading to augmented superoxide production and cell proliferation. These changes were strikingly reversed by administration of human recombinant ACE2, ERK1/2 inhibitor PD98059 and JAK/STAT inhibitor WP1066 but were largely aggravated by pharmacological inhibition of ACE2 with DX600. Taken together, treatment with recombinant ACE2 strikingly prevented Ang II/AT1 receptor-mediated activation of JAK2/STAT3/SOCS3 and profilin-1/ERK1/2 signaling pathways, subsequently contributing to attenuation of superoxide generation and VSMC proliferation.
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Authors
Bei Song, Haiyan Jin, Xi Yu, Zhenzhou Zhang, Huimin Yu, Jing Ye, Yingle Xu, Tong Zhou, Gavin Y. Oudit, Jia-Ying Ye, Chen Chen, Pingjin Gao, Dingliang Zhu, Josef M. Penninger, Jiu-Chang Zhong,