Werner S, Peters K G, Longaker M T, Fuller-Pace F, Banda M J, Williams L T
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6896-900. doi: 10.1073/pnas.89.15.6896.
Recent studies have shown that application of basic fibroblast growth factor (basic FGF) to a wound has a beneficial effect. However, it has not been assessed whether endogenous FGF also plays a role in tissue repair. In this study we found a 160-fold induction of mRNA encoding keratinocyte growth factor (KGF) 1 day after skin injury. This large induction was unique within the family of FGFs, since mRNA levels of acidic FGF, basic FGF, and FGF-5 were only slightly induced (2- to 10-fold) during wound healing, and there was no expression of FGF-3, FGF-4, and FGF-6 detected in normal and wounded skin. High levels of FGF receptor 1 and FGF receptor 2 mRNA and low levels of FGF receptor 3 mRNA were found in both normal and wounded skin. No change in the levels of these transcripts was detected during wound healing. In situ hybridization studies revealed highest levels of KGF mRNA expression in the dermis at the wound edge and in the hypodermis below the wound. In contrast, mRNA encoding the receptor of this growth factor (a splice variant of FGF receptor 2) was predominantly expressed in the epidermis. These results suggest that basal keratinocytes are stimulated by dermally derived KGF during wound healing and implicate a unique role of this member of the FGF family in wound repair.
最近的研究表明,将碱性成纤维细胞生长因子(碱性FGF)应用于伤口具有有益效果。然而,内源性FGF是否也在组织修复中发挥作用尚未得到评估。在本研究中,我们发现皮肤损伤1天后,编码角质形成细胞生长因子(KGF)的mRNA诱导了160倍。这种大幅诱导在FGF家族中是独特的,因为在伤口愈合期间,酸性FGF、碱性FGF和FGF-5的mRNA水平仅轻微诱导(2至10倍),并且在正常和受伤皮肤中未检测到FGF-3、FGF-4和FGF-6的表达。在正常和受伤皮肤中均发现高水平的FGF受体1和FGF受体2 mRNA以及低水平的FGF受体3 mRNA。在伤口愈合期间未检测到这些转录本水平的变化。原位杂交研究显示,在伤口边缘的真皮层和伤口下方的皮下组织中,KGF mRNA表达水平最高。相反,编码该生长因子受体(FGF受体2的一种剪接变体)的mRNA主要在表皮中表达。这些结果表明,在伤口愈合过程中,基底角质形成细胞受到真皮来源的KGF刺激,这暗示了FGF家族的这一成员在伤口修复中具有独特作用。