ROCK1 induces ERK nuclear translocation in PDGF‐BB‐stimulated migration of rat vascular smooth muscle cells

Zhao, Ying; Lv, Miao; Lin, Haishuang; Hong, Yan; Yang, Fuchun; Sun, Yunliang; Guo, Yan; Cui, Ying; Li, Sheng; Gao, Ying

doi:10.1002/iub.598

Cited by 36 publications

(29 citation statements)

References 25 publications

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“…In ROCK1 knockout mice, an open eyelid at birth or omphalocele in neonates was observed (Shimizu et al, 2005), whereas in ROCK2 knockout mice, hemorrhage in embryos or hematoma in embryos and neonates was observed (Thumkeo et al, 2003). Moreover, in vitro studies using Rho-kinase isoform-specific knockdown suggest that ROCK1 and ROCK2 play distinct roles in fibroblasts (Yoneda et al, 2005(Yoneda et al, , 2007, keratinocytes (Lock and Hotchin, 2009;Lock et al, 2012), preadipocytes (Noguchi et al, 2007), adipocytes (Chun et al, 2012), endothelial cells (Mong and Wang, 2009;Bryan et al, 2010;Shimada and Rajagopalan, 2010), vascular smooth muscle cells (Zhao et al, 2012) and cancer cells Inaba et al, 2010;Vega et al, 2011). Other functional differences between ROCK1 and ROCK2 have been reviewed (Noma et al, 2006;Shi and Wei, 2007;Nunes et al, 2010;Satoh et al, 2011).…”

Section: Cytoplasmmentioning

confidence: 99%

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Iizuka

Kimura

Wang

et al. 2012

Cell Struct. Funct.

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ABSTRACT. The small GTP-binding protein Rho plays a crucial role in a wide variety of cellular functions through various effector proteins. Rho-kinase is a key effector protein of Rho, which is composed of two isoforms, ROCK1 and ROCK2. To clarify the site of action of ROCK1 and ROCK2, we performed immunofluorescence and immunoelectron microscopic analyses using isoform-specific antibodies in mouse tissues. In the large and small intestines, ROCK1 immunoreactivity was predominantly identified in epithelial cells, and ROCK2 immunoreactivity was negligible. In these epithelial cells, ROCK1 immunoreactivity was distributed on plasma membranes, while ROCK1 immunogold signals were localized at cell-cell contacts and cell adhesion sites, especially at the adherens junctions at the ultrastructural level. In the bladder epithelium, however, ROCK1 and ROCK2 signals were identified at intermediate filaments, and ROCK2 signals were also observed in nuclei. In the three types of muscular cells-smooth, cardiac, and skeletal muscle cells-ROCK1 and ROCK2 also showed differential distribution. ROCK1 signals were localized at actin filaments, plasma membranes, and vesicles near plasma membranes in smooth muscle cells; at the lysosomes in skeletal muscle cells; and were undetectable in cardiac muscle cells. ROCK2 signals were localized at actin filaments and centrosomes in smooth muscle cells, at intercalated discs in cardiac muscle cells, and at Z-discs and sarcoplasmic reticulum in skeletal muscle cells. In the brain, ROCK1 immunoreactivity was distributed in glia, whereas ROCK2 immunoreactivity was observed in neurons. These results indicate that the two isoforms of Rho-kinase distribute differentially to accomplish their specific functions.

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Section: Cytoplasmmentioning

confidence: 99%

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Iizuka

Kimura

Wang

et al. 2012

Cell Struct. Funct.

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“…However, few studies have explored any potential cross talk between each of these signaling systems. A few studies have shown that ROCK 1 deficiency can impair MAPK signaling, however, little is known regarding the effects of ERK1/2-MAPK deficiency on the ROCK 1 signaling pathway1845. The current work indicates that upon exposure to TGF-β, ERK1/2 phosphorylation in cardiac fibroblasts increases within 30 mins, and that the application of the ERK1/2 phosphorylation inhibitor PD98059 inhibits ROCK 1 and MRTF-A nuclear translocation.…”

Section: Discussionmentioning

confidence: 65%

“…The MAPK pathway is activated by TGF-β in myofibroblasts and is a known downstream factor of TGF-β that mediates ROCK 1 expression in tissues1819.…”

mentioning

confidence: 99%

ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation

Luo

Hieu

et al. 2017

Sci Rep

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Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis.

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“…A signalling pathway between PKCs and mitogen-activated protein kinase (MAPK) seems crucial for the initiation and progression of VSMC proliferation. For example, mitogens can activate MAPK via inducing the kinase translocation from the cytosome to the nucleus where it promotes gene expression and cell growth in undifferentiated cultured VSMCs as well as in differentiated contractile VSM [4], and attenuation of the MAPK pathway by Labedipinedilol-A can inhibit cell proliferation, which is regulated by Ca 2+ and PKC [5]. The PKC family is generally divided into three groups, differing in the enzymes' cofactor requirements: conventional (c) PKCs (including α, β I, II and γ isoforms) require calcium and diacylglycerol (DAG) for activation; novel (n) PKCs (comprising δ, θ, ε and η isoforms) are activated by DAG; and atypical (a) PKCs include ζ and λ/ι isoforms and are dependent on phosphatidylserine but are not affected by DAG, phorbol ester, or Ca…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Protein Kinase C-ε by Prolonged Incubation with PMA Inhibits the Proliferation of Vascular Smooth Muscle Cells

Zhou

Wang

Zhou

et al. 2016

Cell Physiol Biochem

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Background/Aims: Phorbol myristate acetate (PMA) exerts a pleiotropic effect on the growth and differentiation of various cells. Protein kinase Cs (PKCs) plays a central role in mediating the effects of PMA on cells. The present study investigated whether the down-regulation of protein kinase C-ε (PKC-ε) is involved in the inhibition of vascular smooth muscle cell (VSMC) proliferation caused by prolonged PMA incubation. Methods: Using cell counting, Cell Counting Kit-8 (CCK-8) and EdU incorporation assay on VSMCs, we evaluated the inhibitory effects of prolonged incubation of PMA, of lentiviruses carrying the short-hairpin RNAs (shRNA) of PKC-ε and of the PKC-ε inhibitor peptide on the proliferation and viability of cells. The effect of PKC-ε down-regulation on growth of rat breast cancer SHZ-88 cells was also measured. Results: The prolonged incubation of VSMCs with PMA for up to 72 hours resulted in attenuated cell growth rates in a time-dependent manner. The expression of PKC-ε, as assessed by Western blotting, was also decreased accordingly. Notably, the number of EdU-positive cells and the cell viability of VSMCs were decreased by shRNA of PKC-ε and the PKC-ε inhibitor peptide, respectively. The proliferation of rat breast cancer SHZ-88 cells was also attenuated by lentivirus-induced shRNA silencing of PKC-ε. Conclusions: Prolonged incubation of PMA can inhibit the expression of PKC-ε. The effect results in the inhibition of VSMC proliferation. PKC-ε silencing can also attenuate breast cancer cell growth, suggesting that PKC-ε may be a potential target for anti-cancer drugs.

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ROCK1 induces ERK nuclear translocation in PDGF‐BB‐stimulated migration of rat vascular smooth muscle cells

Cited by 36 publications

References 25 publications

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation

Down-Regulation of Protein Kinase C-ε by Prolonged Incubation with PMA Inhibits the Proliferation of Vascular Smooth Muscle Cells

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