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Platelet-derived growth factor (PDGF) stimulates many of the processes important in tissue repair, including proliferation of fibroblasts and synthesis of extracellular matrices. In this study we have demonstrated with in situ hybridization and immunocytochemistry the reversible expression of c-sis/PDGF-2 and PDGF receptor (PDGF-R) b mRNAs and their respective protein products in epithelial cells and fibroblasts following cutaneous injury in pigs. Epithelial cells in control, unwounded skin did not express c-sis and PDGF-R mRNAs, and fibroblasts expressed only PDGF-R mRNA. The expression levels in the injured site were correlated with the stage of tissue repair, being highest during the initial stages of the repair process and declining at the time of complete re-epithelialization and tissue remodeling. It is suggested that the controlled, reversible expression of a potent mitogen and its receptor induced by injury may function in an autocrine/paracrine manner on both epithelial cells and fibroblasts to bring about their sustained proliferation during the normal healing process. These studies provide a molecular basis for understanding the mechanisms contributing to normal tissue repair. We suggest the possibility that a defect in these mechanisms may be associated with defective wound healing. It is also conceivable that "chronic" injury may induce irreversible gene expression leading to pathologic, unregulated cell growth.