Mitogenic Influence of Human R-Spondin1 on the Intestinal Epithelium
2005
Kim, Kyung-Ah | Kakitani, Makoto | Zhao, Jingsong | Oshima, Takeshi | Tang, Tom | Binnerts, Minke | Liu, Yi | Boyle, Bryan | Park, E (Emily) | Emtage, Peter | Funk, Walter D. | Tomizuka, Kazuma
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 {szligbeta}-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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