title: Subcellular distribution patterns and elevated expression of GNA11 and GNA14 proteins in the lungs of humans with pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH), a progressive and devastating disease, is characterized by abnormal proliferation of pulmonary artery endothelial and smooth muscle cells. GTP-binding protein subunits, GNA11 and GNA14, transmembrane and intracellular signaling molecules, participate in the regulating endothelial function and vascular development. We followed the expression of GNA11 and GNA14 in human lungs in control and PAH patients using immunohistochemical and Western blot analyses. Both GNA11 and GNA14 were expressed in lung tissue, primarily in artery endothelial and smooth muscle cells. Expression was more pronounced in PAH lung tissues compared with controls. Using immunocytochemistry and laser scanning confocal microscopy, the subcellular distribution of GNA11 and GNA14 in human pulmonary arterial endothelial (HPAECs) and smooth muscle (HPASMCs) cells in culture was investigated. GNA11 was predominantly localized in the cytoplasm and nucleus of HPASMCs, but it was only found in the cytoplasm of HPAECs. On the other hand, GNA14 immunolocalized to the nucleus and cytoplasm of both HPAECs and HPASMCs. Based on bioinformatic analyses, nuclear localization signal and transmembrane topology confirm the different subcellular distributions of GNA11 and GNA14. The data suggest that GNA11 and GNA14 are related to PAH pathogenesis, and help further functional studies of these proteins in this severe disease.
authors.affiliation: Cardiovascular Disease Laboratory, Department of Cardiovascular Medicine, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, 524000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.forename: Puwen
authors.initials: P
authors.lastname: Chen
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Yue
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Shui
authors.forename: Guoming
authors.initials: G
authors.lastname: Li
authors.forename: Liangqing
authors.initials: L
authors.lastname: Zhang
authors.forename: Shian
authors.initials: S
authors.lastname: Huang
authors.forename: Can
authors.initials: C
authors.lastname: Chen
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D020869:Gene Expression Profiling; D006330:Heart Defects, Congenital / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C554062:GNA11 protein, human; D044385:GTP-Binding Protein alpha Subunits; C119109:GNA14 protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: GNA11; GNA14; endothelial cell; pulmonary arterial hypertension; smooth muscle cells