{"@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/1363951795961244288.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.0805159106"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.0805159106"}}],"dc:title":[{"@value":"R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/β-catenin pathway"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt/β-catenin signaling. We injected recombinant RSpo1 protein into transgenic Wnt reporter TOPGAL mice and have identified the oral mucosa as a target tissue for RSpo1. Administration of RSpo1 into normal mice triggered nuclear translocation of β-catenin and resulted in increased basal layer cellularity, thickened mucosa, and elevated epithelial cell proliferation in tongue. We herein evaluated the therapeutic potential of RSpo1 in treating chemotherapy or radiotherapy-induced oral mucositis in several mouse models. Prophylactic treatment with RSpo1 dose-dependently overcame the reduction of basal layer epithelial cellularity, mucosal thickness, and epithelial cell proliferation in tongues of mice exposed to whole-body irradiation. RSpo1 administration also substantially alleviated tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of tongue ulceration in mice receiving a single fraction, high dose head-only radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and keratinocyte growth factor resulted in complete healing of tongue ulcers in mice subjected to snout-only irradiation. In conclusion, our results demonstrate RSpo1 to be a potent therapeutic agent for oral mucositis by enhancing basal layer epithelial regeneration and accelerating mucosal repair through up-regulation of Wnt/β-catenin pathway.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380576120779673857","@type":"Researcher","foaf:name":[{"@value":"Jingsong Zhao"}],"jpcoar:affiliationName":[{"@value":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120779673859","@type":"Researcher","foaf:name":[{"@value":"Kyung-Ah Kim"}],"jpcoar:affiliationName":[{"@value":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120779673856","@type":"Researcher","foaf:name":[{"@value":"Josephine De Vera"}],"jpcoar:affiliationName":[{"@value":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120779673861","@type":"Researcher","foaf:name":[{"@value":"Servando Palencia"}],"jpcoar:affiliationName":[{"@value":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120779673858","@type":"Researcher","foaf:name":[{"@value":"Marie Wagle"}],"jpcoar:affiliationName":[{"@value":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}]},{"@id":"https://cir.nii.ac.jp/crid/1380576120779673860","@type":"Researcher","foaf:name":[{"@value":"Arie Abo"}],"jpcoar:affiliationName":[{"@value":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2009-02-17","prism:volume":"106","prism:number":"7","prism:startingPage":"2331","prism:endingPage":"2336"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.0805159106"}],"createdAt":"2009-01-30","modifiedAt":"2022-04-12","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360565168790706432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Oral Lining Mucosa Development Depends on Mesenchymal microRNAs"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567183378808960","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"LIG4 mediates Wnt signalling-induced radioresistance"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567184738729728","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Oocyte‐derived R‐spondin2 promotes ovarian follicle development"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848659261067136","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1361415748538316672","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"R-spondin signaling as a pivotal regulator of tissue development and homeostasis"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.0805159106"},{"@type":"CROSSREF","@value":"10.1177/0022034512470830_references_DOI_Fj57eHozdeu3eoT5Si0MOerSghL"},{"@type":"CROSSREF","@value":"10.1038/ncomms10994_references_DOI_Fj57eHozdeu3eoT5Si0MOerSghL"},{"@type":"CROSSREF","@value":"10.1096/fj.12-223412_references_DOI_Fj57eHozdeu3eoT5Si0MOerSghL"},{"@type":"CROSSREF","@value":"10.1084/jem.20101559_references_DOI_Fj57eHozdeu3eoT5Si0MOerSghL"},{"@type":"CROSSREF","@value":"10.1016/j.jdsr.2019.03.001_references_DOI_Fj57eHozdeu3eoT5Si0MOerSghL"}]}