Thrombin induces MCP-1 expression through Rho-kinase and subsequent p38MAPK/NF-κB signaling pathway activation in vascular endothelial cells

Kawanami, Daiji; Matoba, Keiichiro; Kanazawa, Yasushi; Ishizawa, Shin; Yokota, Tamotsu; Utsunomiya, Kazunori

doi:10.1016/j.bbrc.2011.07.031

Cited by 48 publications

(41 citation statements)

References 33 publications

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“…As two isoforms of ROCK in mammalian cells, ROCK1 and ROCK2 share 65% overall identity and 92% identity in the kinase domain, respectively. Previous literatures demonstrated that Rho/Rho kinase (ROCK) pathway is involved in NF-кB activation and plays a pivotal role in LPS-induced inflammatory dysfunction [32,33]. The present data clearly displayed that EVD significantly suppressed the expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κB p65 in ethanolinduced mice.…”

Section: Discussionsupporting

confidence: 64%

Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway

Zhao

Gong

Wang

et al. 2015

International Immunopharmacology

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Section: Discussionsupporting

confidence: 64%

Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway

Zhao

Gong

Wang

et al. 2015

International Immunopharmacology

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“…Subsequent recognition of NF-B by karyopherin ␤ directs it to the nuclear pore complex, where nuclear translocation takes place (14). Evidence exists for a link between Rho-kinase and NF-B activation, and we have recently demonstrated that thrombin activates endothelial NF-B in a Rho-kinase-dependent fashion (17). Moreover, Rho-kinase also plays a role in mediating lysophosphatidic acid-induced NF-B activation in endothelial cells (43) and has been implicated in neuropeptide-induced NF-B activation and subsequent stimulation of IL-8 expression in colonic epithelial cells (50).…”

Section: Discussionmentioning

confidence: 94%

Rho-kinase regulation of TNF-α-induced nuclear translocation of NF-κB RelA/p65 and M-CSF expression via p38 MAPK in mesangial cells

Matoba

Kawanami

Tsukamoto

et al. 2014

American Journal of Physiology-Renal Physiology

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The small GTPase Rho and its downstream effector, Rho-associated coiled-coil containing protein kinase (Rho-kinase), regulate a number of cellular processes, including organization of the actin cytoskeleton, cell adhesion, and migration. While pharmacological inhibitors of Rhokinase signaling are known to block renal inflammation, the molecular basis for this effect is unclear. Here, we provide evidence that proinflammatory TNF-␣ promotes mesangial expression of macrophage colony-stimulating factor (M-CSF), a key regulator for the growth and differentiation of mononuclear phagocytes, in a Rhokinase-dependent manner. Consistent with this observation, TNF-␣-mediated renal expression of M-CSF in insulin-resistant db/db mice was downregulated by Rho-kinase inhibition. Small interfering RNAfacilitated knockdown of Rho-kinase isoforms ROCK1 and ROCK2 indicated that both isoforms make comparable contributions to regulation of M-CSF expression in mesangial cells. From a mechanistic standpoint, Western blotting and EMSA showed that Rho-kinase and its downstream target p38 MAPK regulate nuclear translocation of NF-B RelA/p65 and subsequent DNA binding activity, with no significant effects on IB␣ degradation and RelA/p65 phosphorylation. Moreover, we showed that Rho-kinase-mediated cytoskeletal organization is required for the nuclear uptake of RelA/p65. Collectively, these findings identify Rho-kinase as a critical regulator of chemokine expression and macrophage proliferation.

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“…This study provided new insight on the role of Rho-kinase, demonstrating that Rho-kinase may regulate intracellular translocation of transcriptional factors, likely through re-organization of actin stress fibers. Finally, we have shown that Rhokinase blockade attenuates other microvascular complications such as diabetic retinopathy [56] and neuropathy [57], as well as atherosclerosis [58]. Importantly, the effect of Rho-kinase inhibitors on diabetic complications is independent of glucose and blood pressure [51,53].…”

Section: Vldl Ldl Idlmentioning

confidence: 93%

Dyslipidemia in diabetic nephropathy

2016

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Diabetic nephropathy (DN) not only is a major cause of end-stage renal disease (ESRD) in developing and developed countries but also plays a critical role as a risk factor for cardiovascular disease. The pathogenesis of DN is multifactorial and remains to be elucidated. It is well known that dyslipidemia is frequently complicated with diabetes. Recently, dyslipidemia has been recognized to be involved in the progression of DN. In general, diabetic dyslipidemia is caused by impaired action of lipoprotein lipase (LPL) that is localized to the endothelial cells, resulting in increased serum levels of increased triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C). Smaller size and modified low-density lipoprotein (LDL), such as glycated and oxidized LDL, play important roles to induce vascular and renal cellular dysfunction. Previous studies demonstrated that dyslipidemia enhances macrophage infiltration and excessive extracellular matrix (ECM) production in the glomeruli under diabetic conditions, leading to the development of DN. Clinical studies have demonstrated that lipid-lowering therapy shows a protective effect on the renal function. It is well known that statins reduce albuminuria in patients with DN. A series of our studies indicated that this effect is mediated by Rho-kinase inhibition. Rho-kinase plays a key role in the pathogenesis of DN by activating the inflammatory pathway, including oxidative stress, NF-κB, and hypoxia inducible factor (HIF)-1. Intriguingly, Rho-kinase inhibitors have been shown to attenuate glomerulosclerosis as well as atherosclerosis. Therefore, Rho-kinase could be a promising therapeutic target for both DN and cardiovascular disease.

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Thrombin induces MCP-1 expression through Rho-kinase and subsequent p38MAPK/NF-κB signaling pathway activation in vascular endothelial cells

Cited by 48 publications

References 33 publications

Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway

Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway

Rho-kinase regulation of TNF-α-induced nuclear translocation of NF-κB RelA/p65 and M-CSF expression via p38 MAPK in mesangial cells

Dyslipidemia in diabetic nephropathy

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