TRANSFORMING GROWTH-FACTOR-BETA UP-REGULATES THE EXPRESSION OF THE GENES FOR BETA-4 INTEGRIN AND BULLOUS PEMPHIGOID ANTIGENS (BPAG1 AND BPAG2) IN NORMAL AND TRANSFORMED HUMAN KERATINOCYTES

Three distinct proteins, namely, beta4 integrins, and the 230-kDa (BPAG1) and 180-kDa (BPAG2) bullous pemphigoid antigens, have been shown to co-localize with hemidesmosomes at the dermal-epidermal basement membrane zone. In this study, we examined the expression of the corresponding genes in cultures of normal and transformed human epidermal keratinocytes. The expression of these genes was detected by Northern and in situ hybridizations, and the expression of beta4 integrins was also demonstrated by indirect immunofluorescence. The results indicated clearly detectable expression of all three genes in normal keratinocytes, whereas extremely low or undetectable levels of expression were noted in two transformed cell lines. Addition of TGF-beta1 or TGF-beta2 (10 ng/ml) up-regulated mRNA levels for all three proteins (up to 4.6 times). The increase by TGF-beta1 was particularly striking in keratinocyte cultures incubated in the presence of low (0.15 mM) Ca++, and somewhat less pronounced in the presence of high (1.2 mM) Ca++. The increase in beta4 integrin synthesis was also documented by enhanced immunosignal of the corresponding epitopes. These results indicate that the three hemidesmosomal genes studied here are all responsive to TGF-beta. These observations, together with previous data on the effects of TGF-beta on other components of the skin, suggest that this cytokine may play a role in the development and repair of the cutaneous basement membrane zone.