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Enhanced anti-apoptosis and gut epithelium protection function of acidic fibroblast growth factor after cancelling of its mitogenic activity.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2004 Dec 15; Vol. 10 (24), pp. 3590-6. - Publication Year :
- 2004
-
Abstract
- Aim: Mitogenic and non-mitogenic activities of fibroblast growth factor (FGF) are coupled to a range of biological functions, from cell proliferation and differentiation to the onset of many diseases. Recent reports have shown that acidic fibroblast growth factor (aFGF) has a powerful anti-apoptosis function, which may have potentially therapeutical effect on gut ischemia and reperfusion injuries. However, whether this function depends on its mitogenic or non-mitogenic activity remains unclear. In this study, we identified the source of its anti-apoptosis function with a mutant, aFGF28-154 and observed its effect on reducing gut ischemia and reperfusion injury.<br />Methods: aFGF28-154 was generated by amplification of appropriate DNA fragments followed by subcloning the products into pET-3c vectors, then they were expressed in BL21 (DE3) cells and purified on an M2 agarose affinity column. This mutant aFGF28-154 maintained its non-mitogenic activity and lost its mitogenic activity. With a dexamethasone (DEX)-induced mouse thymocyte apoptosis model in vitro and in vivo, we studied the anti-apoptotic function of aFGF28-154. Also, in vivo study was performed to further confirm whether aFGF28-154 could significantly reduce apoptosis in gut epithelium after gut ischemia-reperfusion injury in rats. Based on these studies, the possible signal transduction pathways involved were studied.<br />Results: With a dexamethasone (DEX)-induced mouse thymocyte apoptosis model in vitro and in vivo, we found that the anti-apoptotic function of aFGF28-154 was significantly enhanced when compared with the wild type aFGF. In vivo study further confirmed that aFGF28-154 significantly reduced apoptosis in gut epithelium after gut ischemia-reperfusion injury in rats. The mechanisms of anti-apoptosis function of aFGF28-154 did not depend on its mitogenic activity and were mainly associated with its non-mitogenic activities, including the intracellular calcium ion balance protection, ERK1/2 activation sustaining and cell cycle balance.<br />Conclusion: These findings emphasize the importance of non-mitogenic effects of aFGF, and have implications for its therapeutic use in preventing apoptosis and other injuries in tissues and internal organs triggered by ischemia-reperfusion injury.
- Subjects :
- Animals
Apoptosis physiology
Cell Division drug effects
Cell Division physiology
Dexamethasone pharmacology
Fibroblast Growth Factor 1 genetics
Glucocorticoids pharmacology
Intestinal Mucosa drug effects
Mice
Mice, Inbred BALB C
NIH 3T3 Cells
PC12 Cells
Plasmids
Rats
Reperfusion Injury pathology
Signal Transduction drug effects
Signal Transduction physiology
Thymus Gland cytology
Apoptosis drug effects
Fibroblast Growth Factor 1 pharmacology
Intestinal Mucosa cytology
Mitogens pharmacology
Reperfusion Injury drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1007-9327
- Volume :
- 10
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 15534912
- Full Text :
- https://doi.org/10.3748/wjg.v10.i24.3590