Effect of mobilization bone marrow stem cells on hypoxia inducible factor-1α and epidermal growth factor in rats with renal injury induced by ischemic reperfusion

Abstract

Objective To investigate the mobilization of granulocyte-colony stimulating factor(G-CSF) with stem cell factor(SCF) in bone marrow stem cells(BMSC), and to observe the therapeutic effects of BMSC mobilization on repairing ischemia/reperfusion(I/R) renal injury induced by hypoxia inducible factor-1α(HIF-1α) and epidermal growth factor(EGF), and to investigate the mechanism for BMSC mobilization for repairing I/R renal injury. Methods One hundred and sixty male Sprague-Dawley rats(age: 8-10 weeks) were randomly allocated into 4 groups(40 rats in each group): control group(group A), I/R group(group B), SCF+ G-CSF treatment group(group C) and SCF+ G-CSF control group(group D). The expressions of CD34+ and EGF were measured by immunohistochemistry technique, and the expression of EGF mRNA was measured by reverse transcriptase-polymerase chain reaction. Results 1.After I/R injury, the renal tubular epithelial cells were in a state of degeneration, necrosis, even exfoliation.As the time prolonged, the necrotic renal tubules were repaired gradually, but the repair in group C was not good compared with that in group B. The level of group C was obviously lower than that of group B on the 5th, 10th, 17th and 24th day(P 0.05). On 5 d postoperative, the level of CD34+ cells of group B and group C was conspicuous higher than group A and D(P<0.05), and that of group C was conspicuous higher than that of group B(P<0.05). They descended gradually from the 5th day with the time prolonged.3.The expressions of HIF-1α of group B and group C had a highly positive reaction on the 5th day postoperatively and the level of HIF-1α of group B and group C decended to the normal level with the time prolonged, and at each time, the expression of HIF-1α of group C was significantly higher than that of other groups(P<0.05).4.On the 5th day postoperative, the expression of EGF of group B and group C showed a higher positive reaction on the 5th day postoperatively and the level of EGF in group B and group C descended to the normal level with the time prolonged, and at each time the expression of EGF of group C was significantly higher than that of the other groups(P<0.05).5.The expressions of EGF mRNA of group B and C showed higher positive reaction on the 5th day postoperatively(P<0.05). The level of EGF mRNA of group B was higher significantly than that of group A on the 17th day posto-peratively(P<0.05). The level of EGF mRNA of group C was a peak and higher than that of other groups on the 10th day postoperatively(P<0.05). The level of EGF of group B and group C descended to a normal level with the time prolonged.6.There was a positive correlation between the expressions of HIF-1α and EGF(r=0.815, P<0.01). Conclusions Combination of SCF with the mobilization of G-CSF sufficiently homed BMSC to injured renal tissue was an important factor for the recovery of injured renal tubules.Combination of SCF with G-CSF may promote the expression of HIF-1α and EGF in the kidney may be one of the mechanisms of why combination of SCF with G-CSF can promote recovery from renal ischemic reperfusion injury. Key words: Bone marrow stem cell; Ischemic reperfusion, renal; Hypoxia inducible factor-1α; Epidermal growth factor; Rat