TY - JOUR
T1 - Enhanced proliferation of cultured human vascular smooth muscle cells linked to increased function of RNA-binding protein HuR
AU - Pullmann, Rudolf
AU - Juhaszova, Magdalena
AU - López De Silanes, Isabel
AU - Kawai, Tomoko
AU - Mazan-Mamczarz, Krystyna
AU - Halushka, Marc K.
AU - Gorospe, Myriam
PY - 2005/6/17
Y1 - 2005/6/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20744441183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20744441183&partnerID=8YFLogxK
U2 - 10.1074/jbc.M501106200
DO - 10.1074/jbc.M501106200
M3 - Article
C2 - 15824116
AN - SCOPUS:20744441183
SN - 0021-9258
VL - 280
SP - 22819
EP - 22826
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -