Rho-associated protein kinase isoforms stimulate proliferation of vascular smooth muscle cells through ERK and induction of cyclin D1 and PCNA
Copyright policy )Rho-associated protein kinase isoforms stimulate proliferation of vascular smooth muscle cells through ERK and induction of cyclin D1 and PCNA
Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) plays an important role in vascular diseases. The Rho-associated protein kinase (ROCK) signaling pathway is now well recognized for its role in VSMC migration and proliferation. Recently, a number of studies revealed that different isoforms of ROCK have distinct functions in VSMCs. We have reported that ROCK1, rather than ROCK2, induces platelet-derived growth factor (PDGF)-BB-stimulated migration of VSMCs. In the current study, we aimed to investigate the roles of ROCK1/2 in PDGF-induced rat aorta VSMC proliferation by manipulating ROCK gene expression. The results revealed that knock-down of both ROCK1 and ROCK2 by siRNA technology decreased PDGF-BB-generated VSMC proliferation by inhibiting the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1. In addition, up-regulation of ROCK1 expression through transfection, further increased the proliferation of VSMCs induced by PDGF-BB. The ERK inhibitor U0126 reduced the proliferation and expression of PCNA and cyclinD1, and ROCK1 and ROCK2 siRNA decreased the level of ERK in the nucleus. These results demonstrated that ROCK1 and ROCK2 could promote VSMC proliferation through ERK nuclear translocation, regulating the expression of PCNA and cyclin D1 protein.
- MRC Laboratory of Molecular Biology United Kingdom
- Medical Research Council United Kingdom
- Gunma University Japan
- Dalian Medical University China (People's Republic of)
Cell Nucleus, rho-Associated Kinases, Pyridines, Myocytes, Smooth Muscle, Active Transport, Cell Nucleus, Becaplermin, Proto-Oncogene Proteins c-sis, Amides, Muscle, Smooth, Vascular, Rats, Isoenzymes, Gene Knockdown Techniques, Proliferating Cell Nuclear Antigen, Animals, Cyclin D1, Vascular Diseases, Enzyme Inhibitors, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Cell Proliferation
Cell Nucleus, rho-Associated Kinases, Pyridines, Myocytes, Smooth Muscle, Active Transport, Cell Nucleus, Becaplermin, Proto-Oncogene Proteins c-sis, Amides, Muscle, Smooth, Vascular, Rats, Isoenzymes, Gene Knockdown Techniques, Proliferating Cell Nuclear Antigen, Animals, Cyclin D1, Vascular Diseases, Enzyme Inhibitors, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Cell Proliferation
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