Article

Mitogenic influence of human R-spondin1 on the intestinal epithelium

Nuvelo, Inc., 675 Almanor Avenue, Sunnyvale, CA 94085, USA.
Science (Impact Factor: 31.48). 09/2005; 309(5738):1256-9. DOI: 10.1126/science.1112521
Source: PubMed

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.

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    • "2012). Rspo1 has been implicated in many adult stem cell in vitro expansion systems, such as the intestine, stomach , and liver (Kim et al. 2005; Sato et al. 2009; Barker et al. 2010; Huch et al. 2013). However, it remains unclear in vivo which cells produce Rspo proteins in these organs. "
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    • "Rspo1-null mice have decreased fertility and lack duct branching and alveolar formation in the mammary glands, leading to a failure of lactation (Chadi et al., 2009). Systemic administration of Rspo1 in mice leads to a dramatic enlargement of the gastrointestinal tract with extensive proliferation of the crypt epithelial cells (Kim et al., 2005). "
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    • "This tissue is known to be strictly dependent on Wnt signals for its homeostatic proliferation , as removal of Wnt components (Korinek et al, 1998; van Es et al, 2012) or introduction of Wnt inhibitors (Pinto et al, 2003; Kuhnert et al, 2004) abrogates this proliferation. Introduction of the Wnt potentiator R-spondin1 induces crypt hyperplasia (Kim et al, 2005b). Briefly, intestinal crypts were isolated from murine small intestines by EDTA-elution after removal of the intestinal villi. "
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