Enhanced proliferation of cultured human vascular smooth muscle cells linked to increased function of RNA-binding protein HuR.
In dividing cells, the RNA-binding protein HuR associates with and stabilizes labile mRNAs encoding proliferative proteins, events that are linked to the increased cytoplasmic presence of HuR. Here, assessment of HuR levels in various vascular pathologies (intimal hyperplasia, atherosclerosis and neointimal proliferation, sclerosis of arterialized saphenous venous graft, and fibromuscular dysplasia) revealed a distinct increase in HuR expression and cytoplasmic abundance within the intima and neointima layers. On the basis of these observations, we postulated a role for HuR in promoting the proliferation of vascular smooth muscle cells. To test this hypothesis directly, we investigated the expression, subcellular localization, and proliferative influence of HuR in human vascular smooth muscle cells (hVSMCs). Treatment of hVSMCs with platelet-derived growth factor increased HuR levels in the cytoplasm, thereby influencing the expression of metabolic, proliferative, and structural genes. Importantly, knockdown of HuR expression by using RNA interference caused a reduction of hVSMC proliferation, both basally and following platelet-derived growth factor treatment. We propose that HuR contributes to regulating hVSMC growth and homeostasis in pathologies associated with vascular smooth muscle proliferation.
Pullmann
Rudolf
R
Laboratory of Cellular and Molecular Biology and Laboratory of Cardiovascular Sciences, NIA-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Juhaszova
Magdalena
M
López de Silanes
Isabel
I
Kawai
Tomoko
T
Mazan-Mamczarz
Krystyna
K
Halushka
Marc K
MK
Gorospe
Myriam
M
D000954:Antigens, Surface / Q000737:chemistry*; D019921:Biotinylation; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D000954:Antigens, Surface; D018076:DNA, Complementary; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012313:RNA