title: Rho-associated protein kinase isoforms stimulate proliferation of vascular smooth muscle cells through ERK and induction of cyclin D1 and PCNA.
abstract: 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.
authors: Key Laboratory of Molecular Biology of Liaoning Province, Dalian Medical University, Dalian 116044, China.
authors: Ying
authors: Y
authors: Zhao
authors: Miao
authors: M
authors: Lv
authors: HaiShuang
authors: H
authors: Lin
authors: Ying
authors: Y
authors: Cui
authors: XiaoQing
authors: X
authors: Wei
authors: YuanHua
authors: Y
authors: Qin
authors: Kazuhiro
authors: K
authors: Kohama
authors: Ying
authors: Y
authors: Gao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000577:Amides / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D002467:Cell Nucleus / Q000201:enzymology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014652:Vascular Diseases / Q000201:enzymology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D019938:Cyclin D1; C108830:Y 27632; D000077214:Becaplermin; C578418:ROCK1 protein, rat; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases