Inhibition of dermal fibrosis in self-assembled skin equivalents by undifferentiated keratinocytes

Abstract

Background: Previous studies showed that keratinocyte plays a major role in dermal cell behavior and hypertrophic scar formation. Further investigations showed that keratinocytes derived from normal skin and hypertrophic scar have different effects on dermal fibroblasts.

Objective: To investigate the role of undifferentiated keratinocytes in epidermal-dermal interaction and dermal fibrosis.

Methods: A tissue-engineered model of self-assembled reconstructed skin was used in this study to mimic interactions between dermal and epidermal cells. Transmission electron microscope, RT and Western blot analysis were performed to show extracellular matrix morphology, collagen synthesis and associated factors expression changes.

Results: The dermal extracellular matrix co-cultured with undifferentiated keratinocytes was well distributed, collagen bundles were not seen, and the levels of collagen mRNA and protein expression declined to 46%, 20% of that in the presence of differentiated keratinocytes. Undifferentiated keratinocytes inhibited dermal fibrosis through down-regulation of TGFbeta1, promoting bFGF expression and desmosome formation.

Conclusions: Undifferentiated keratinocytes have the ability to preserve normal epidermal-dermal interaction and inhibit dermal fibrosis. Absence or diminution of undifferentiated keratinocytes may take part in initiating events leading to pathological fibrosis.