Mitogenic influence of human R-spondin1 on the intestinal epithelium.
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.
Kim
Kyung-Ah
KA
Nuvelo, Inc., 675 Almanor Avenue, Sunnyvale, CA 94085, USA.
Kakitani
Makoto
M
Zhao
Jingsong
J
Oshima
Takeshi
T
Tang
Tom
T
Binnerts
Minke
M
Liu
Yi
Y
Boyle
Bryan
B
Park
Emily
E
Emtage
Peter
P
Funk
Walter D
WD
Tomizuka
Kazuma
K
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002678:Chimera; D003106:Colon / Q000166:cytology / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019858:Enteroendocrine Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005472:Fluorouracil / Q000009:adverse effects; D004763:Glucagon-Like Peptides; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000166:cytology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008934:Mitogens; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014059:Tongue / Q000187:drug effects / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; D000098907:R-Spondins
D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005472:Fluorouracil; D004763:Glucagon-Like Peptides; D008934:Mitogens; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; D019699:Thrombospondins; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; C503243:RSPO1 protein, human; D000098907:R-Spondins; C015236:glucagon-like-immunoreactivity