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.

Keywords

CryptEpitheliumWnt signaling pathwayIntestinal epitheliumBiologyCell growthGastrointestinal epitheliumCell biologyCancer researchMolecular biologySignal transductionEndocrinologyBiochemistryGenetics

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Year
2005
Type
article
Volume
309
Issue
5738
Pages
1256-1259
Citations
575
Access
Closed

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Kyung‐Ah Kim, Makoto Kakitani, Jingsong Zhao et al. (2005). Mitogenic Influence of Human R-Spondin1 on the Intestinal Epithelium. Science , 309 (5738) , 1256-1259. https://doi.org/10.1126/science.1112521

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DOI
10.1126/science.1112521