{"@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/1360021390749854336.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/ijms241411355"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/1422-0067/24/14/11355/pdf"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Enhanced Levels of Glycosphingolipid GM3 Delay the Progression of Diabetic Nephropathy"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>We recently found that albuminuria levels in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) inversely correlate with glycosphingolipid GM3 expression levels in glomerular podocytes. Moreover, we showed enhanced expression of GM3 via activation of the GM3 synthase gene upon administration of valproic acid (VPA) is effective in suppressing albuminuria and podocyte injury in mice with anti-nephrin antibody-induced podocytopathy. However, the therapeutic effect of GM3 on diabetic nephropathy, which is the most common underlying disease in patients undergoing dialysis and with podocyte injury, remains unclear. Here, we investigated the therapeutic effect of enhanced GM3 expression via VPA on podocyte injury using streptozotocin-induced diabetic nephropathy model mice. Administration of VPA clearly decreased levels of albuminuria and glomerular lesions and inhibited the loss of podocytes and expansion in the mesangial area. Furthermore, we found that albuminuria levels in patients with diabetic nephropathy inversely correlate with the expression of GM3 in podocytes. These results indicate that maintaining GM3 expression in podocytes by administration of VPA may be effective in treating not only podocyte injury, such as MCD and FSGS, but also the late stage of diabetic nephropathy.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420564276185008768","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"40365101"},{"@type":"NRID","@value":"1000040365101"},{"@type":"NRID","@value":"9000016405549"}],"foaf:name":[{"@value":"Shokichi Naito"}],"jpcoar:affiliationName":[{"@value":"Department of Nephrology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara 252-0374, Kanagawa, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390749854218","@type":"Researcher","foaf:name":[{"@value":"Kenichi Nakayama"}],"jpcoar:affiliationName":[{"@value":"National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba 305-8560, Ibaraki, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390749854215","@type":"Researcher","foaf:name":[{"@value":"Nagako Kawashima"}],"jpcoar:affiliationName":[{"@value":"Department of Nephrology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara 252-0374, Kanagawa, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14220067"}],"prism:publicationName":[{"@value":"International Journal of Molecular Sciences"}],"dc:publisher":[{"@value":"MDPI AG"}],"prism:publicationDate":"2023-07-12","prism:volume":"24","prism:number":"14","prism:startingPage":"11355"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://www.mdpi.com/1422-0067/24/14/11355/pdf"}],"createdAt":"2023-07-13","modifiedAt":"2025-10-10","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=glycosphingolipid%20GM3;%20valproic%20acid;%20diabetic%20nephropathy;%20albuminuria;%20podocyto%20injury","dc:title":"glycosphingolipid GM3; valproic acid; diabetic nephropathy; albuminuria; podocyto injury"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256977306752","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"18K08249"},{"@type":"JGN","@value":"JP18K08249"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K08249/"}],"notation":[{"@language":"ja","@value":"正常ポドサイトにおける細胞膜分子・糖脂質GM3の重要性"},{"@language":"en","@value":"Importance of glycolipid GM3 on cell membrane of podocytes"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004236408931712","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL/6 Mouse Strain"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011142936513280","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous 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focal segmental glomerulosclerosis inhibited by enhanced glycosphingolipid GM3 via valproic acid"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021392639998080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Single‐cell\n                    <scp>RNA</scp>\n                    ‐seq with spatial transcriptomics to create an atlas of human diabetic kidney disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021397010692480","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"How Many Cell Types Are in the Kidney and What Do They Do?"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285712902535296","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Glycosphingolipid metabolic reprogramming drives neural differentiation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619941660672","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292620913032064","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Human melanoma antigen AH is an autoantigenic ganglioside related to GD2."}]},{"@id":"https://cir.nii.ac.jp/crid/1360292621129794944","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Enhanced insulin sensitivity in mice lacking ganglioside GM3"}]},{"@id":"https://cir.nii.ac.jp/crid/1360298341433675648","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Pathophysiology of mesangial expansion in diabetic nephropathy: mesangial structure, glomerular biomechanics, and biochemical signaling and 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DIABETES"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346466220800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ganglioside GM3 inhibits the high glucose- and TGF-β1-induced proliferation of rat glomerular mesangial cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346467102592","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Renal cell markers: lighthouses for managing renal diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848656086560256","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Deletion of platelet-derived growth factor receptor-β improves diabetic nephropathy in Ca2+/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569266159616","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Transcriptional activation of human GM3 synthase (hST3Gal V) gene by valproic acid in ARPE-19 human retinal pigment epithelial cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861293105026560","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861707121031424","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Glycosphingolipid GM3 prevents albuminuria and podocytopathy induced by anti-nephrin antibody"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861713865858944","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Decreases of ganglioside GM3 in streptozotocin-induced diabetic glomeruli of rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865817570464128","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Molecular pathways that drive diabetic kidney disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818224223872","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Targeting the Pathobiology of Diabetic Kidney Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818225009152","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Up-Date on Diabetic Nephropathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820083126656","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cellular crosstalk of glomerular endothelial cells and podocytes in diabetic kidney disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865821263328000","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044695434752","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Epidermal growth factor receptor tyrosine kinase is modulated by GM3 interaction with N-linked GlcNAc termini of the receptor"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044956251264","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A vital role for glycosphingolipid synthesis during development and differentiation"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045443501568","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A role for glycosphingolipid accumulation in the renal hypertrophy of streptozotocin-induced diabetes mellitus."}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520047015168","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Podocyte Biology and Pathogenesis of Kidney 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Detection and characterisation by mouse monoclonal antibody."}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468900554112","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Update of pathophysiology and management of diabetic kidney disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981469274300544","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Induction of Glycosphingolipid GM3 Expression by Valproic Acid Suppresses Cancer Cell Growth"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670319861708672","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Tyrosine Kinase Activity of Epidermal Growth Factor Receptor Is Regulated by GM3 Binding through Carbohydrate to Carbohydrate Interactions"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670321180620160","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Podocytopathies"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951796239625216","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Soluble FLT1 Binds Lipid Microdomains in Podocytes to Control Cell Morphology and Glomerular Barrier Function"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233270579051904","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cancer-Associated Glycosphingolipid Antigens: Their Structure, Organization, and Function"}]},{"@id":"https://cir.nii.ac.jp/crid/2050307417120962816","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Histochemical and immunoelectron microscopic analysis of ganglioside GM3 in human kidney"}]},{"@id":"https://cir.nii.ac.jp/crid/2050307417131910784","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Decreased GM3 correlates with proteinuria in minimal change nephrotic syndrome and focal segmental glomerulosclerosis"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.3390/ijms241411355"},{"@type":"KAKEN","@value":"PRODUCT-24854841"},{"@type":"OPENAIRE","@value":"doi_dedup___::b88c76d7d94d4e5ad93664fd5958b09a"},{"@type":"CROSSREF","@value":"10.1038/s41598-023-49684-z_references_DOI_JyUsCvyqTM99OJzkel7DkMwVwrM"}]}