AIM:Mitogenic and non-mitogenic activities of fibroblastgrowth factor (FGF) are coupled to a range of biologicalfunctions,from cell proliferation and differentiation to theonset of many diseases.Recent reports have shown thatacidic fibrobtast growth factor (aFGF) has a powerful anti-apoptosis function,which may have potentially therapeuticaleffect on gut ischemia and reperfusion injuries.However,whether this function depends on its mitogenic or non-mitogenic activity remains unclear.In this study,we identifiedthe source of its anti-apoptosis function with a mutant,aFGF28-154 and observed its effect on reducing gut ischemiaand reperfusion injury.METHODS:aFGF28-154 was generated by amplificationof appropriate DNA fragments followed by subcloning theproducts into pET-3c vectors,then they were expressed inBL21 (DE3) cells and purified on an M2 agarose affinity column.This mutant aFGF28-154 maintained its non-mitogenicactivity and lost its mitogenic activity.With a dexamethasone(DEX)-induced mouse thymocyte apoptosis model in vitroand in vivo,we studied the anti-apoptotic function ofaFGF28-154.Also,in vivo study was performed to furtherconfirm whether aFGF28-154 could significantly reduceapoptosis in gut epithelium after gut ischemia-reperfusioninjury in rats.Based on these studies,the possible signaltransduction pathways involved were studied.RESULTS:With a dexamethasone (DEX)-induced mousethymocyte apoptosis model in vitro and in vivo,we foundthat the anti-apoptolJc function of aFGF28-154 was significantlyenhanced when compared with the wild type aFGF.In vivostudy further confirmed that aFGF28-154 significantlyreduced apoptosis in gut epithelium after gut ischemia-reperfusion injury in rats.The mechanisms of anti-apoptosisfunction of aFGF28-154 did not depend on its mitogenicactivity and were mainly associated with its non-mitogenicactivities,including the intracellular calcium ion balanceprotection,ERK1/2 activation sustaining and cell cycle balance. CONCLUSION:These findings emphasize the importance ofnon-mitogenic effects of aFGF,and have implications for itstherapeutic use in preventing apoptosis and other injuries intissues and internal organs triggered by ischemia-reperfusioninjury. AIM: Mitogenic and non-mitogenic activities of fibroblast growth factor (FGF) are coupled to a range of biologicalfunctions, from cell proliferation and differentiation to the onset of many diseases.Recent reports have shown thatacidic fibroblast growth factor (aFGF) has a powerful anti-apoptosis function, which may have potentially therapeutic effect on gut ischemia and reperfusion injuries. Whether, this 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. METHODS: aFGF28-154 was generated by amplification of the 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) -induce d 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 reduceapoptosis in gut epithelium after gut ischemia-reperfusioninjury in rats.Based on these studies, the possible signaltraction pathways involved were studied.RESULTS: With a dexamethasone (DEX) -induced mouse thymocyte apoptosis model in vitro and in vivo, we found that the anti-apoptolJc function of aFGF28-154 was significantly enhanced when compared with the wild type aFGF . In vivostudy further confirmed that aFGF28-154 significantlyreduced apoptosis in gut epithelium after gut ischemia-reperfusion injury in rats. The mechanisms of anti-apoptosisfunction of aFGF28-154 did not depend on its mitogenic activity and were mainly associated with its non-mitogenicactivities, including the intracellular calcium ion balance protein, ERK1 / 2 activation sustaining and cell cycle balance. CONCLUSION: Thesefindings emphasizes the importance of non-mitogenic effects of aFGF, and have implications for it stherapeutic use in preventing apoptosis and other injuries intissues and internal organs triggered by ischemia-reperfusion in jury.