角质细胞生长因子2对细胞生长、移行及创伤愈合的作用

Effects of Keratinocyte Growth Factor 2(KGF-2) on Keratinocyte Growth,Migration and on Excisional Wound Healing

角质细胞生长因子2(KGF-2)是成纤维细胞生长因子超家族的一员,由间质细胞合成并分泌,能特异促进上皮细胞增殖、分化与迁移,对脊椎动物多种组织和器官的发育起重要调控作用.通过PCR从人的肾组织cDNA文库中克隆分离获得了KGF-2的cDNA,表明该因子在成人肾中有表达.采用大肠杆菌表达并纯化重组蛋白用于生物学功能研究的结果显示:KGF-2在体外不仅能够促进角质细胞的生长和增殖,而且对其凋亡具有抑制作用,还对细胞的移行具有影响.在动物实验中,KGF-2能促进皮肤切除产生的伤口愈合,提示该蛋白质可以作为创伤治疗或辅助用药的候选分子.

Keratinocyte growth factor 2 （KGF-2） is a member of the FGF family that is mainly synthesized by mesenchymal cells and acts 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.