title: The cross talk between cGMP signal pathway and PKC in pulmonary endothelial cell angiogenesis.
abstract: Angiogenic proliferation of vascular endothelial cells is believed to play an important role in pulmonary vascular remodeling in pulmonary arterial hypertension. In the present study, we found that c-GMP (cyclic guanosine monophosphate) inhibited the proliferation and tube formation of pulmonary vascular endothelial cells induced by TGF-β1, and that this process was reversed by PKG (protein kinase G) inhibitor and PKC (protein kinase C) inhibitor. In addition, small interfering RNA (siRNA) targeting ERK also reduced cellular proliferation. Furthermore, western blotting showed that cGMP down-regulated the phosphorylation level of ERK1/2, which was reversed not only by PKG inhibitor but also by PKC inhibitor. Silencing different PKC isoforms showed that PKCΔ, PKCγ and PKCα were involved in ERK phosphorylation, suggesting that PKC kinases have a permissive action. Three subtypes, PKCΔ, PKCγ and PKCα are likely to be involved the phosphorylation suppression of ERK included cGMP. Taken together, these data suggest that ERK phosphorylation mediates the proliferation of pulmonary vascular endothelial cells, and PKC kinases have a permissive action in this process.
authors.affiliation: Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. zaczeng@163.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. daisycui0128@126.com.
authors.forename: Ying-Chuan
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. zz73cxf@sohu.com.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Jiao
authors.affiliation: Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 18930173652@189.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. zlxsh4808@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D020935:MAP Kinase Signaling System; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D011493:Protein Kinase C; D006152:Cyclic GMP