083 Transforming Growth Factor‐Beta Ligand, Receptor, and SMAD Expression Patterns in Fetal and Adult Keratinocytes

Abstract

Listen

Translate article

Introduction: The transforming growth factor‐beta (TGF‐ß) cytokine family regulates cellular proliferation, differentiation, and migration with important function during both development and repair. Moreover, the TGF‐ßs are growth inhibitory for keratinocytes, proliferative for fibroblasts, and generally profibrotic during repair. In order to better define the influence of keratinocyte TGF‐ß during these processes, we examined the TGF‐ß isoform, receptor, and signal messenger Smad expression in fetal and postnatal keratinocytes. Methods: Sprague‐Dawley rat keratinocytes were isolated in primary culture from fetal at E15 and E17 (term = E22), newborn, and 6 week old adults. Open fetal rat wounds heal without scar at E17 gestation. Quantitative‐polymerase chain reaction was performed for TGF‐ß1, ‐ß2, and ‐ß3 ligand; TGF‐beta receptor1 and ‐receptor2; Smad3, Smad4, and Smad7 expression. All cells were passage 2 or 3. Results: TGF‐ß1 expression did not change appreciably from E15 to adult age in keratinocytes. TGF‐ß2 and ‐ß3 expression increased (8 fold and 2 fold respectively) from E17 to newborn ages. Overall, the expression of TGF‐ß1 was 5–8 fold greater compared to ‐ß2 and ‐ß3 in both fetal and adult keratinocytes. TGF‐ß receptor1 expression increased 2 fold whereas ‐receptor2 expression showed little change from E17 to adult age. Smad3 expression increased over 50 fold, with Smads 4 and 7 showing a smaller increase from E17 to adult age. Conclusions: The TGF‐beta system has differential expression in fetal compared to postnatal keratinocytes, which suggests function during skin differentiation. TGF‐ß1 expression is relatively greater than ‐ß2 and ‐ß3 in both fetal and adult keratinocytes. However, increases in isoforms ‐ß2 and ‐ß3, receptor1 and the Smads occurs at ages associated with scarring, implying increased function of the pro‐fibrotic TGF‐beta response during ages associated with scarring.