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Activation of AMPK inhibits pulmonary arterial smooth muscle cells proliferation. 2014

Yuanyuan Wu, and Lu Liu, and Yonghong Zhang, and Guizuo Wang, and Dong Han, and Rui Ke, and Shaojun Li, and Wei Feng, and Manxiang Li
Department of Respiratory Medicine, Respiratory Diseases Research Center, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.

The aims of the present study were to examine the effect of AMPK activation on pulmonary arterial smooth muscle cells (PASMCs) proliferation and to address its potential mechanisms. ET-1 dose and time-dependently induced PASMCs proliferation, and this effect was suppressed by a selective AMPK activator metformin. The results of the study further indicated that the proliferation of PASMCs stimulated by ET-1 was associated with the increase of Skp2 and decrease of p27, and metformin reversed ET-1-induced Skp2 elevation and raised p27 protein level. Our study suggests that activation of AMPK suppresses PASMCs proliferation and has potential value in negatively modulating pulmonary vascular remodeling and therefore could prevent or treat the development of pulmonary arterial hypertension (PAH).

UI MeSH Term Description Entries
D008687 Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289) Dimethylguanylguanidine,Dimethylbiguanidine,Glucophage,Metformin HCl,Metformin Hydrochloride,HCl, Metformin,Hydrochloride, Metformin
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011651 Pulmonary Artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Arteries, Pulmonary,Artery, Pulmonary,Pulmonary Arteries
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D044786 S-Phase Kinase-Associated Proteins A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS. S-Phase Kinase Associated Protein,SCF(SKP2),Skp Domain Protein,Skp Domain Proteins,Skp1 Protein,Skp1 Proteins,Skp2 Protein,Skp2 Proteins,p19 SKP1,p19(SKP1) Protein,p45 SKP2,p45(SKP2),p45(SKP2) Protein,Kinase-Associated Proteins, S-Phase,Proteins, S-Phase Kinase-Associated,S Phase Kinase Associated Protein,S Phase Kinase Associated Proteins,SKP1, p19,SKP2, p45
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D050760 Cyclin-Dependent Kinase Inhibitor p27 A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2. CDK Inhibitor p27,CDKN1B Protein,CDKN4 Protein,Cyclin-Dependent Kinase Inhibitor 1B,p27 CDK Inhibitor,p27 Kip1 Protein,p27Kip1 Protein,CDK Inhibitor, p27,Cyclin Dependent Kinase Inhibitor 1B,Cyclin Dependent Kinase Inhibitor p27,Kip1 Protein, p27,p27, CDK Inhibitor

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