PDGF-induced proliferation in human arterial and venous smooth muscle cells: molecular basis for differential effects of PDGF isoforms. 2011

Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
Division of Nephrology & Hypertension, University of Utah, Salt Lake City, UT, USA. li.li@hsc.utah.edu

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of arterial atherosclerosis and venous neointimal hyperplasia. We examined the effects of PDGF isoforms on smooth muscle cells (SMCs) from arterial and venous origins in order to further understand the differential responsiveness of these vasculatures to proliferative stimuli. Serum-starved human arterial and venous SMCs exhibited very different proliferative responses to PDGF isoforms. Whereas, proliferation of arterial SMCs was strongly stimulated by PDGF-AA, venous SMCs showed no proliferative response to PDGF-AA, but instead demonstrated a significantly greater proliferative response to PDGF-BB than arterial SMCs. Part of this difference could be attributed to differences in PDGF receptors expression. There was a 2.5-fold higher (P < 0.05) density of PDGF receptor-α (PDGF-Rα) and a 6.6-fold lower (P < 0.05) density of PDGF-Rβ expressed on arterial compared to venous SMCs. Concomitant with an increased proliferative response to PDGF-AA in arterial SMCs was a marked PDGF-Rα activation, enhanced phosphorylation of ERK1/2 and Akt, a transient activation of c-Jun NH2-terminal kinase (JNK), and a significant reduction in expression of the cell-cycle inhibitor p27(kip1). This pattern of signaling pathway changes was not observed in venous SMCs. No phosphorylation of PDGF-Rα was detected after venous SMC exposure to PDGF-AA, but there was enhanced phosphorylation of ERK1/2 and Akt in venous SMCs, similar to that seen in the arterial SMCs. PDGF-BB stimulation of venous SMC resulted in PDGF-Rβ activation as well as transactivation of epidermal growth factor receptor (EGF-R); transactivation of EGF-R was not observed in arterial SMCs. These results may provide an explanation for the differential susceptibility to proliferative vascular diseases of arteries and veins.

UI MeSH Term Description Entries
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
D010982 Platelet-Derived Growth Factor Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. Platelet Derived Growth Factor,Factor, Platelet-Derived Growth,Growth Factor, Platelet-Derived
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001158 Arteries The vessels carrying blood away from the heart. Artery
D014680 Veins The vessels carrying blood away from the CAPILLARY BEDS. Vein
D017479 Receptors, Platelet-Derived Growth Factor Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types. PDGF Receptors,Platelet-Derived Growth Factor Receptors,Receptors, PDGF,PDGF Receptor,Platelet-Derived Growth Factor Receptor,Platelet Derived Growth Factor Receptor,Platelet Derived Growth Factor Receptors,Receptor, PDGF,Receptors, Platelet Derived Growth Factor
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
D050759 Cyclin-Dependent Kinase Inhibitor p21 A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3. CDK2-Associated Protein 20 kDa,CDKN1 Protein,CDKN1A Protein,Cdk-Interacting Protein 1,Cdk2 Inhibitor Protein,Cell Cycle Regulator p21,Cyclin Kinase Inhibitor p21,Cyclin-Dependent Kinase Inhibitor 1A Protein,Senescent Cell-Derived Inhibitor Protein 1,p21 Cell Cycle Regulator,p21 Cyclin Kinase Inhibitor,CDK2 Associated Protein 20 kDa,Cdk Interacting Protein 1,Cyclin Dependent Kinase Inhibitor 1A Protein,Cyclin Dependent Kinase Inhibitor p21,Senescent Cell Derived Inhibitor Protein 1
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

Related Publications

Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
November 2012, Respiratory research,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
January 2007, The international journal of biochemistry & cell biology,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
May 1995, Biochemical Society transactions,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
August 2008, Free radical biology & medicine,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
October 2018, Experimental cell research,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
May 1989, Biochemical and biophysical research communications,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
August 2015, Experimental cell research,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
March 1996, The American journal of physiology,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
May 2016, Pharmacological research,
Li Li, and Donald K Blumenthal, and Christi M Terry, and Yuxia He, and Mary L Carlson, and Alfred K Cheung
January 2019, International journal of clinical and experimental pathology,
Copied contents to your clipboard!