Mitogenic influence of human R-spondin1 on the intestinal epithelium |
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| Authors: | Kim Kyung-Ah Kakitani Makoto Zhao Jingsong Oshima Takeshi Tang Tom Binnerts Minke Liu Yi Boyle Bryan Park Emily Emtage Peter Funk Walter D Tomizuka Kazuma |
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| Institution: | Nuvelo, Inc., 675 Almanor Avenue, Sunnyvale, CA 94085, USA. |
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| Abstract: | Several described growth factors influence the proliferation and regeneration of the intestinal epithelium. Using a transgenic mouse model, we identified a human gene, R-spondin1, with potent and specific proliferative effects on intestinal crypt cells. Human R-spondin1 (hRSpo1) is a thrombospondin domain-containing protein expressed in enteroendocrine cells as well as in epithelial cells in various tissues. Upon injection into mice, the protein induced rapid onset of crypt cell proliferation involving beta-catenin stabilization, possibly by a process that is distinct from the canonical Wnt-mediated signaling pathway. The protein also displayed efficacy in a model of chemotherapy-induced intestinal mucositis and may have therapeutic application in gastrointestinal diseases. |
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