{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004232000112640.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.bbrc.2010.10.093"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0006291X10019820?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0006291X10019820?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"20977889"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Rho-kinase mediates TNF-α-induced MCP-1 expression via p38 MAPK signaling pathway in mesangial cells"}],"description":[{"notation":[{"@value":"Macrophage accumulation has been implicated in the pathogenesis of inflammatory glomerular disease. Monocyte chemoattractant protein-1 (MCP-1) plays a central role in recruiting monocytes to the glomeruli. Tumor necrosis factor-α (TNF-α) has been shown to induce MCP-1 expression in mesangial cells, although the precise mechanisms remain unclear. We previously demonstrated that RhoA and its effector, Rho-kinase (Rho-associated coiled-coil containing protein kinase, ROCK), are involved in the pathogenesis of diabetic nephropathy. However, its role in MCP-1 induction by TNF-α has not been elucidated. In the present study, we investigated whether the Rho/Rho-kinase signaling pathway regulates the TNF-α-mediated induction of MCP-1 in mesangial cells. Exposure of mouse mesangial cells (MES-13) to TNF-α resulted in an increase of MCP-1 expression (by RT-PCR) and secretion into the medium (by ELISA). Pull down and Western blot analysis revealed that TNF-α activated RhoA and Rho-kinase. Based on these observations, we speculated that the Rho/Rho-kinase signaling pathway may be involved in MCP-1 induction by TNF-α. In agreement with this concept, Y-27632, a specific Rho-kinase inhibitor, attenuated TNF-α-mediated induction of MCP-1. We demonstrated that Y-27632 inhibited TNF-α-mediated monocyte migration and attenuated TNF-α-mediated p38 MAPK activation. Based on these data we infer that Y-27632 inhibits TNF-α-induced MCP-1 expression, secretion and function through inhibition of Rho-kinase and p38 MAPK activity. Our study suggests that Rho/Rho-kinase is an important therapeutic target of monocyte recruitment and accumulation within the glomerulus in inflammatory renal disease."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004232000112642","@type":"Researcher","foaf:name":[{"@value":"Keiichiro Matoba"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004232000112640","@type":"Researcher","foaf:name":[{"@value":"Daiji Kawanami"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004232000112641","@type":"Researcher","foaf:name":[{"@value":"Sho Ishizawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004232000112645","@type":"Researcher","foaf:name":[{"@value":"Yasushi Kanazawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004232000112643","@type":"Researcher","foaf:name":[{"@value":"Tamotsu Yokota"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004232000112644","@type":"Researcher","foaf:name":[{"@value":"Kazunori Utsunomiya"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"0006291X"}],"prism:publicationName":[{"@value":"Biochemical and Biophysical Research Communications"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2010-11","prism:volume":"402","prism:number":"4","prism:startingPage":"725","prism:endingPage":"730"},"reviewed":"false","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0006291X10019820?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0006291X10019820?httpAccept=text/plain"}],"createdAt":"2010-10-26","modifiedAt":"2025-09-13","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=rho-Associated%20Kinases","dc:title":"rho-Associated Kinases"},{"@id":"https://cir.nii.ac.jp/all?q=Pyridines","dc:title":"Pyridines"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Necrosis%20Factor-alpha","dc:title":"Tumor Necrosis Factor-alpha"},{"@id":"https://cir.nii.ac.jp/all?q=Chemotaxis","dc:title":"Chemotaxis"},{"@id":"https://cir.nii.ac.jp/all?q=Amides","dc:title":"Amides"},{"@id":"https://cir.nii.ac.jp/all?q=p38%20Mitogen-Activated%20Protein%20Kinases","dc:title":"p38 Mitogen-Activated Protein Kinases"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Glomerulonephritis","dc:title":"Glomerulonephritis"},{"@id":"https://cir.nii.ac.jp/all?q=Mesangial%20Cells","dc:title":"Mesangial Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Enzyme%20Inhibitors","dc:title":"Enzyme Inhibitors"},{"@id":"https://cir.nii.ac.jp/all?q=Chemokine%20CCL2","dc:title":"Chemokine CCL2"},{"@id":"https://cir.nii.ac.jp/all?q=Signal%20Transduction","dc:title":"Signal Transduction"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782124748800","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22590900"},{"@type":"JGN","@value":"JP22590900"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590900/"}],"notation":[{"@language":"ja","@value":"糖尿病性腎症発症機転における Rho/ROCK 系シグナル制御機構の検討"},{"@language":"en","@value":"Role of Rh/Rho-kinase pathway in the pathogenesis of diabetic nephropathy"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002215311416576","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Neurotrophic and neuroprotective properties of exendin-4 in adult rat dorsal root ganglion neurons: involvement of insulin and 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