Publication Date:
2005-08-20
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Kyung-Ah -- Kakitani, Makoto -- Zhao, Jingsong -- Oshima, Takeshi -- Tang, Tom -- Binnerts, Minke -- Liu, Yi -- Boyle, Bryan -- Park, Emily -- Emtage, Peter -- Funk, Walter D -- Tomizuka, Kazuma -- New York, N.Y. -- Science. 2005 Aug 19;309(5738):1256-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nuvelo, Inc., 675 Almanor Avenue, Sunnyvale, CA 94085, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16109882" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antineoplastic Agents/adverse effects
;
Cell Line
;
Cell Line, Tumor
;
*Cell Proliferation
;
Chimera
;
Colon/cytology/pathology
;
Cytoskeletal Proteins/metabolism
;
Dose-Response Relationship, Drug
;
Enteroendocrine Cells/metabolism
;
Epithelial Cells/metabolism
;
Fibroblast Growth Factor 7
;
Fibroblast Growth Factors/pharmacology
;
Fluorouracil/adverse effects
;
Glucagon-Like Peptides
;
Humans
;
Intestinal Mucosa/*cytology/metabolism/pathology
;
Intestine, Small/cytology/pathology
;
Mice
;
Mice, Transgenic
;
*Mitogens
;
Neoplasm Transplantation
;
Neoplasms, Experimental/drug therapy/pathology
;
Peptides/pharmacology
;
Proteins/pharmacology
;
Recombinant Proteins/pharmacology
;
Thrombospondins/genetics/metabolism/pharmacology/*physiology
;
Tongue/drug effects/pathology
;
Trans-Activators/metabolism
;
Wnt Proteins
;
Wnt3 Protein
;
beta Catenin
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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