TRANSFORMING GROWTH-FACTOR-BETA STIMULATES THE EXPRESSION OF DESMOSOMAL PROTEINS IN BRONCHIAL EPITHELIAL-CELLS

Transforming growth factor-beta(1) (TGF-beta(1)) has been shown to induce squamous differentiation of cultured airway epithelial cells. It has also been shown to increase expression of matrix proteins and integrin receptors in cell culture of these and other cells. However, it is unknown if TGF-beta(1) affects expression of genes encoding intercellular junctional proteins. Therefore, we have investigated the effect of TGF-beta(1) on the expression of proteins and mRNAs for desmoplakins (DPs) I and II, desmosomal plaque proteins. Fibronectin, known to be induced by TGF-beta(1) was used as a positive control and tubulin as a negative control. Twenty-four hours after TGF-beta(1) stimulation, DP I and II mRNA levels assessed by Northern blotting analysis had increased significantly (DP I mRNA, 1.8-fold, P < 0.05; DP II mRNA, 2.4-fold, P < 0.04), thereby indicating pretranslational regulation of DP expression. By comparison, mRNA for fibronectin increased 8.1-fold whereas mRNA for tubulin was unchanged. Immunofluorescence using the monoclonal anti-DP I and II antibodies revealed dramatic increased expression of punctate DP structures after exposure to TGF-beta(1). Immunoblot analyses with polyclonal anti-DP I antibodies showed increased levels of both DP I (250 kD) and DP II (215 kD), with the DP I increase being more pronounced (DP I, 2.5-fold; DP II, 1.4-fold at 48 h relative to controls), suggesting translational regulation by TGF-beta(1). This study therefore demonstrates the ability of TGF-beta(1) to alter cellular phenotype by altering expression of proteins involved in intercellular junctions. Alteration of the expression of such proteins may be an important feature of TGF-beta(1)-induced cellular differentiation.