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 γ-irradiation, and peak levels were observed from 48 to 120 h after irradiation. At all times after irradiation, the higher molecular mass isoform (∼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.

Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis

“…[29][30][31] Each of these factors has been described earlier as facilitating intestinal mucosa repair, either through enhancement of cell proliferation or inhibition of epithelial cell apoptosis, or by a combination of both. [32][33][34][35] The therapeutic benefit of MSC reported in this study could be the consequence of releases and synergic effects of multiple paracrine factors. Further research is needed to elucidate this complex issue.…”

Blockade of CXCL10 protects mice from acute colitis and enhances crypt cell survival

“…A multistep migratory process of epithelial cells is pivotal to steady-state tissue homeostasis and mucosal protection, since impaired migration often leads to intestinal disorders, including IBD and also neoplasm [26,27]. Although several growth factors may contribute to the multistep processes by stimulating proliferation or maturation of the epithelial cells [21,24,28], the mechanisms regulating hierarchical positioning and in vivo migration of epithelial cells are not fully understood.…”

Effects of Basic Fibroblast Growth Factor on Radiation-Induced Proliferation Inhibition and Apoptosis in Thymocytes and Splenocytes

“…[1][2][3][4][5] The radioprotective effects of FGF, especially bFGF, on skin and bone marrow in vivo were also documented. [6][7][8][9][10] The present study was the first time to explore the protection by bFGF against radiationinduced proliferation inhibition and apoptotic effects in the splenocytes and thymocytes of mice wholebody X-ray irradiated with 0.5 or 1.0 Gy (clinically relevant doses). We found that bFGF did not provide significant protection when splenocytes and thymocytes were irradiated in vivo and incubated with bFGF in vitro at the current concentrations.…”

“…6) Third, bFGF was given in vitro after irradiation in the present study, while previous studies that indicated protective effects were predominantly obtained in in vivo animal studies. 6,7,9,16) For example, Gallicchio et al, 6) demonstrated that when combined with adherent cell-depleted normal murine marrow cells, FGF increased the number of both day 9 and day 12 spleen CFUs from lethally irradiated animals. In adherent cell depleted murine and human marrow cultures, the addition of FGF showed synergistic activity in combination with the optimal concentration of GM-colony-stimulating factor (CSF) for CFU-GM.…”

“…Studies [6][7][8][9][10] have shown that bFGF enhances the survival of a variety of endothelial, epithelial, and hematopoietic cell lines subjected to ionizing radiation. However, little is known about the effects of bFGF on organs involved in immune regulation such 655-659 (2006) mocyte suspensions were prepared as described in previous studies.…”