TEMPERATURE-SENSITIVE REGULATION OF EPIDERMAL MORPHOGENESIS AND THE EXPRESSION OF CORNIFIED ENVELOPE PRECURSORS BY EGF AND TGF-ALPHA

Epidermis reconstructed on de-epidermized dermis was used to investiga te the effects of growth factors and culture temperature on epidermal morphogenesis and the expression of cornified envelope precursors. Cul tures grown at 33 degrees C or 37 degrees C in the absence or presence of transforming growth factor alpha (TGF alpha), keratinocyte growth factor (KGF), basic fibroblast growth factor (bFGF), or insulin-like g rowth factor (IGF) show a similar morphology to that of native epiderm is. Loricrin and SPRR2 are expressed in the stratum granulosum and SPR R3 is absent. Cultures grown in epidermal growth factor (EGF)-suppleme nted medium at 37 degrees C have a normal morphology, whereas cultures grown at 33 degrees C have a disorganized basal layer, no stratum gra nulosum, and nuclei are present in the stratum corneum. Loricrin is ab sent, and SPRR2 and SPRR3 expression extend into the spinous layers. I rrespective of the culture condition used, involucrin is aberrantly ex pressed in all suprabasal layers. EGF stimulated keratinocyte prolifer ation and migration to a greater degree than TGF alpha. Epidermis reco nstructed on fibroblast-populated collagen gels at 33 degrees C led to the same disturbances in keratinocyte differentiation as seen in cult ures grown on de-epidermized dermis at 33 degrees C in the presence of EGF, whereas parallel cultures grown at 37 degrees C have a similar m orphology to that of native epidermis.