title: cGMP-dependent protein kinase Iα transfection inhibits hypoxia-induced migration, phenotype modulation and annexins A1 expression in human pulmonary artery smooth muscle cells.
abstract: Our previous work has demonstrated that the cellular phenotype changes of human pulmonary artery smooth muscle cells (PASMCs) play an important role during pulmonary vascular remodelling. However, little is known about the role of PASMCs phenotype modulation in the course of hypoxia-induced migration and its behind molecular mechanisms. In this study, we have shown that cGMP-dependent protein kinase (PKG) Iα transfection significantly attenuated the hypoxia-induced down-regulation of the expressions of SM-α-actin, MHC and calponin. Hypoxia-induced PASMC migration was also suppressed by PKGIα overexpression. Furthermore, this overexpression attenuated ANX A1 upregulation under hypoxic conditions. All those effects were reversed by a PKG inhibitor KT5823. Our data indicate that manipulating upstream entity e.g., PKGIa, may have a potential therapeutic value to prevent hypoxia-associated pulmonary arterial remodeling for pulmonary hypertension development.
authors.affiliation: Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Ning
authors.forename: Jianteng
authors.initials: J
authors.lastname: Gu
authors.forename: Guansong
authors.initials: G
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Lu
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017305:Annexin A1 / Q000096:biosynthesis*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000096985:Calponins
chemical_list: D000199:Actins; D017305:Annexin A1; D002135:Calcium-Binding Proteins; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D008840:Microfilament Proteins; D018995:Myosin Heavy Chains; D000096985:Calponins; C541116:ACTA2 protein, human; C569718:PRKG1 protein, human