ABSTRACT
Objective To investigate the therapeutic effect of KGF-2 mutants on radiation-induced intestinal mucosal injury.Methods Specific pathogen free (SPF) female C57BL/6J mice were randomly divided into 4 groups, which were treated with/without KGF2 mutant and/or bone marrow cell transplantation.All the 4 groups were radiated with one-time whole bodyγ-ray exposure of 12 Gy.Also one untreated group was included as control.The therapeutic effect of recombi-nant human KGF-2 mutants on radiation-induced intestinal mucosal injury was analyzed by the survival rate at the 30th day, the pathological change and the apoptosis as well as autophagy status of small intestine at 72 hours after exposure.Results After irradiation, all the mice in the untreated group died within 9 days while the mice treated with KGF-2 mutant combined with bone marrow cell transplantation showed a 70%survival rate at the 30th day.We also found that intestinal mucosa of the mice in this group had a more intact structure, a higher level of autophagy and a lower level of apoptosis via HE staining and immunohistochemistry.Conclusion KGF-2 mutant has a significant therapeutic effect on radiation-induced intestinal mucosal injury.
ABSTRACT
Keratinocyte growth factor 2 (KGF-2) is a member of the FGF family that is mainly synthesized by mesenchymal cells and acta predominantly on epithelial cells in a paracrine manner. It is known to play an important role in fetal limb and lung development; skin wound healing and prostatic epithelial cell growth. The KGF-2 coding sequence were isolated from human kidney cDNA library, revealing that the Kgf-2 gene is also expressed in the kidney apparatus. Purified from prokaryotic E. coli cells, the effects of the recombinant KGF-2 protein in cultured keratinocyte were analyzed by using MTT assay and in situ TUNEL assay. Interestingly, results revealed that KGF-2 promoted keratinocyte cell growth by stimulating cell proliferation and attenuating cell apoptosis. These findings supported a few evidences that KGF-2 could contribute to alveolar epithelial cells against apoptosis. Cell migration assays for the first time revealed that KGF-2 could stimulate keratinocyte cell migration in vitro. In addition, in the pilot animal test, recombinant KGF-2 incorporated within the hydrogel dressing exhibited significantly stimulatory effect on cutaneous wound healing. These combined effects implicate a potential therapeutic application of human recombinant KGF-2 in the future.