Marchese C, Chedid M, Dirsch O R, Csaky K G, Santanelli F, Latini C, LaRochelle W J, Torrisi M R, Aaronson S A
National Institute for Cancer Research, University of Rome La Sapienza, Italy.
J Exp Med. 1995 Nov 1;182(5):1369-76. doi: 10.1084/jem.182.5.1369.
We investigated the expression and distribution of keratinocyte growth factor (KGF) (FGF-7) and its receptor (KGFR) during reepithelialization of human skin. KGF mRNA levels increased rapidly by 8-10-fold and remained elevated for several days. In contrast, KGFR transcript levels decreased early but were significantly elevated by 8-9 d. A KGF-immunoglobulin G fusion protein (KGF-HFc), which specifically and sensitively detects the KGFR, localized the receptor to differentiating keratinocytes of control epidermis, but revealed a striking decrease in receptor protein expression during the intermediate period of reepithelization. Suramin, which blocked KGF binding and stripped already bound KGF from its receptor, failed to unmask KGFRs in tissue sections from the intermediate phase of wound repair. The absence of KGFR protein despite increased KGFR transcript levels implies functional receptor downregulation in the presence of increased KGF. This temporal modulation of KGF and KGFRs provides strong evidence for the functional involvement of KGF in human skin reepithelialization.
我们研究了角质形成细胞生长因子（KGF）（FGF - 7）及其受体（KGFR）在人皮肤再上皮化过程中的表达和分布。KGF mRNA水平迅速增加8 - 10倍，并在数天内保持升高。相比之下，KGFR转录水平早期下降，但在第8 - 9天显著升高。一种能特异性且灵敏地检测KGFR的KGF - 免疫球蛋白G融合蛋白（KGF - HFc），将该受体定位于对照表皮的分化角质形成细胞，但显示在再上皮化的中间阶段受体蛋白表达显著下降。苏拉明可阻断KGF结合并从其受体上剥离已结合的KGF，但未能使伤口修复中间阶段组织切片中的KGFRs暴露出来。尽管KGFR转录水平升高但KGFR蛋白缺失，这意味着在KGF增加的情况下功能性受体下调。KGF和KGFRs的这种时间性调节为KGF在人皮肤再上皮化中的功能性参与提供了有力证据。
