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FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury.

Abstract
Fibroblast growth factors (FGFs) have mitogenic activity toward a wide variety of cells of mesenchymal, neuronal, and epithelial origin and regulate events in normal embryonic development, angiogenesis, wound repair, and neoplasia. FGF-2 is expressed in many normal adult tissues and can regulate migration and replication of intestinal epithelial cells in culture. However, little is known about the effects of FGF-2 on intestinal epithelial stem cells during either normal epithelial renewal or regeneration of a functional epithelium after injury. In this study, we investigated the expression of FGF-2 in the mouse small intestine after irradiation and determined the effect of exogenous FGF-2 on crypt stem cell survival after radiation injury. Expression of FGF-2 mRNA and protein began to increase at 12 h after gamma-irradiation, and peak levels were observed from 48 to 120 h after irradiation. At all times after irradiation, the higher molecular mass isoform ( approximately 24 kDa) of FGF-2 was the predominant form expressed in the small intestine. Immunohistochemical analysis of FGF-2 expression after radiation injury demonstrated that FGF-2 was predominantly found in the mesenchyme surrounding regenerating crypts. Exogenous recombinant human FGF-2 (rhFGF-2) markedly enhanced crypt stem cell survival when given before irradiation. We conclude that expression of FGF-2 is induced by radiation injury and that rhFGF-2 can enhance crypt stem cell survival after subsequent injury.
AuthorsC W Houchen, R J George, M A Sturmoski, S M Cohn
JournalThe American journal of physiology (Am J Physiol) Vol. 276 Issue 1 Pg. G249-58 (01 1999) ISSN: 0002-9513 [Print] United States
PMID9887002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • RNA, Messenger
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
Topics
  • Animals
  • Cell Survival (drug effects)
  • Female
  • Fibroblast Growth Factor 2 (genetics, metabolism, pharmacology)
  • Humans
  • Intestines (drug effects, pathology, radiation effects)
  • Mice
  • Mice, Inbred Strains
  • RNA, Messenger (metabolism)
  • Radiation Injuries, Experimental (metabolism)
  • Recombinant Proteins
  • Stem Cells (drug effects, physiology)
  • Tissue Distribution

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