Induction of fibronectin gene expression by transforming growth factor beta-1 is attenuated in bronchial epithelial cells by ADP-ribosyltransferase inhibitors

✍ Scribed by Joe D. Beckmann; Mary Illig; Debra Romberger; Stephen I. Rennard

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 836 KB
• Volume: 152
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041520208

✦ Synopsis

Transforming growth factor-beta (TGF-P) exerts several effects on cultured airway epithelial cells including inhibition of proliferation and stimulation of fibronectin gene expression. ADP-ribosylation is one potential regulatory mechanism of gene expression by TGF-P. We tested this possibility by exposing cultured bovine bronchial epithelial cells to the chemical inhibitor of ADP-ribosyl transferase enzymes, 3-aminobenramide (3-AB) and, for comparison, 3-aminobenzoic acid (3-ABA), which is structurally similar to 3-A6 but which does not inhibit ADPribosyl transferases. Exponential cell growth rate ( I .2 doublings/day) or cellular morphology observed by phase contrast microscopy were not affected by 3 m M 3-A6 or 3-ABA. Neither compound antagonized inhibition of cell division or induction of squamous morphology by TGF-P1. In contrast, the sixfold stimulation of fibronectin production by exposure of cells to 30 pM TCF-PI for 48 h was reduced by 50% in the presence of 3 mM 3-AB, whereas 3 mM 3-ABA had no effect. The antagonistic effect was augmented by administration of 3-AB 24 h prior to induction by TGF-Pl . Northern blot hybridization analyses demonstrated that 3-AB, but not 3-ABA, attenuated the induction of fibronectin mRNA by TGF-P1 by up to 50%. The5e observations may implicate il role of cellular ADP-ribosylation in the regulation of some gene expression by TGF-P. o I Y Y ~ Wiky ~1 5 5 , Inc.