{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:28:26Z","timestamp":1793042906747,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,2,17]]},"abstract":"<jats:p>R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt\/\u03b2-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 \u03b2-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\/\u03b2-catenin pathway.<\/jats:p>","DOI":"10.1073\/pnas.0805159106","type":"journal-article","created":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T20:34:16Z","timestamp":1233261256000},"page":"2331-2336","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":99,"title":["R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt\/\u03b2-catenin pathway"],"prefix":"10.1073","volume":"106","author":[{"given":"Jingsong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"De Vera","sequence":"additional","affiliation":[{"name":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Servando","family":"Palencia","sequence":"additional","affiliation":[{"name":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Wagle","sequence":"additional","affiliation":[{"name":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Abo","sequence":"additional","affiliation":[{"name":"Department of Research, Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.1.2305"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508324200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701927200"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702305104"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbaexp.2003.10.009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.07.019"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.018"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.02.001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112521"},{"key":"e_1_3_3_10_2","first-page":"3","article-title":"Oral mucositis in cancer therapy","volume":"2","author":"Sonis ST","year":"2004","unstructured":"ST Sonis, Oral mucositis in cancer therapy. 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