Mitogenic influence of human R-spondin1 on the intestinal epithelium

  • Science. 2005 Aug 19;309(5738):1256-9. doi: 10.1126/science.1112521.
Kyung-Ah Kim  1 ,  Makoto Kakitani ,  Jingsong Zhao ,  Takeshi Oshima ,  Tom Tang ,  Minke Binnerts ,  Yi Liu ,  Bryan Boyle ,  Emily Park ,  Peter Emtage ,  Walter D Funk ,  Kazuma Tomizuka
Affiliations
  • 1. Nuvelo, Inc., 675 Almanor Avenue, Sunnyvale, CA 94085, USA.
PMID: 16109882 DOI: 10.1126/science.1112521
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.