1. Mitogenic influence of human R-spondin1 on the intestinal epithelium
- Author
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Kim, Kyung-Ah, Kakitani, Makoto, Zhao, Jingsong, Oshima, Takeshi, Tang, Tom, Binnerts, Minke, Liu, Yi, Boyle, Bryan, Park, Emily, Emtage, Peter, Funk, Walter D., and Tomizuka, Kazuma
- Subjects
Epithelium -- Research ,Colorectal diseases -- Research ,Gastrointestinal diseases -- Research ,Science and technology ,Research - 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 β-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., The intestinal epithelium undergoes rapid and continuous self-renewal along the crypt-villus axis, and the β-catenin/T cell factor (TCF) signal transduction pathway plays a pivotal role in the proliferation, differentiation, and [...]
- Published
- 2005