Transforming growth factor-β up-regulates the expression of the genes for β4 integrin and bullous pemphigoid antigens (BPAG1 and BPAG2) in normal and transformed human keratinocytes

Abstract

Three distinct proteins, namely, β4 integrins, and the 230kDa (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 β4 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-β1 or TGF-β2 (10 ng/ml) up-regulated mRNA levels for all three proteins (up to 4.6 times). The increase by TGF-β1 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 β4 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-β. These observations, together with previous data on the effects of TGF-β 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. © 1992.