Induction of KGF, basic FGF, and TGFalpha mRNA expression during healing of experimental TM perforations.

KGF (KGF), synthesized and secreted exclusively by stromal cells in epithelialized organs, specifically promotes proliferation of cells of epithelial origin, including keratinocytes. A related peptide, basic fibroblast growth factor (bFGF), has mitogenic properties for fibroblasts and endothelial cells. KGF expression is stimulated markedly in the skin during wound healing. To investigate the physiologic action of KGF in the healing of TM (TM) perforations, we examined KGF and KGF receptor (KGFR) mRNA transcript levels as well as those of bFGF and transforming growth factor-alpha (TGFalpha) in normal and wounded rat TM at varying intervals, using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). We found KGF and TGFalpha mRNA expression to be induced rapidly, peaking 3 days after wounding and then declining. Expression of bFGF was induced gradually and remained increased until 7 days. In contrast, we found KGFR to be expressed in normal TM, remaining unchanged during TM repair. These results indicate that KGF and TGFalpha may mediate migration and proliferation of epithelial cells of the outer layer in the early stage of TM repair while bFGF may mediate the connective tissue reaction in the middle layer in a subsequent stage.