Differential expression of receptor tyrosine kinases and Shc in fetal and adult rat fibroblasts: Toward defining scarless versus scarring fibroblast phenotypes

The remarkable ability of the fetus to heal early gestation skin wounds wit hout scarring remains poorly understood. Taking advantage of recent advance s in signal transduction, the tyrosine phosphorylation patterns of fetal ra t fibroblasts, representing the scarless cutaneous repair phenotype, and ad ult rat fibroblasts, representing scar-forming phenotype, were examined whe ther there were inherent differences in cellular signaling. Specifically, c orrelation of the phosphorylation patterns with the expression levels of th e signaling molecules that transmit information from the plasma membrane re ceptor to the nucleus was sought. By using three different cell lines of ex planted fibroblasts from gestational day 13 fetal rat skin (n = 24) and 1-m onth-old postnatal adult rat skin (n = 3), immunoblotting was performed to compare tyrosine phosphorylation patterns. The results revealed five major protein bands of interest in fetal rat fibroblasts, but not in the adult ra t fibroblasts. These phosphorylated protein bands are of interest because o f their possible role in wound repair and may have the potential to regulat e cellular responses to the extracellular matrix and their secondary signal ing molecules. It was hypothesized that these bands represented receptor ty rosine kinases, epidermal growth factor receptor, and discoidin domain rece ptor 1, and their downstream adaptor protein Shc that binds receptor tyrosi ne kinases to transduce signals intracellularly. Furthermore, elevated expr ession of platelet-derived growth factor receptor-beta in adult compared wi th fetal fibroblasts was demonstrated, suggesting that decreased expression of certain growth factors may also be important for the scarless phenomeno n to occur.