Induction of fibronectin gene expression by transforming growth factor beta-1 is attenuated in bronchial epithelial cells by ADP-ribosyltransferase inhibitors.
Transforming growth factor-beta (TGF-beta) 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-beta. We tested this possibility by exposing cultured bovine bronchial epithelial cells to the chemical inhibitor of ADP-ribosyl transferase enzymes, 3-aminobenzamide (3-AB) and, for comparison, 3-aminobenzoic acid (3-ABA), which is structurally similar to 3-AB but which does not inhibit ADP-ribosyl transferases. Exponential cell growth rate (1.2 doublings/day) or cellular morphology observed by phase contrast microscopy were not affected by 3 mM 3-AB or 3-ABA. Neither compound antagonized inhibition of cell division or induction of squamous morphology by TGF-beta 1. In contrast, the sixfold stimulation of fibronectin production by exposure of cells to 30 pM TGF-beta 1 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-beta 1. Northern blot hybridization analyses demonstrated that 3-AB, but not 3-ABA, attenuated the induction of fibronectin mRNA by TGF-beta 1 by up to 50%. These observations may implicate a role of cellular ADP-ribosylation in the regulation of some gene expression by TGF-beta.
Beckmann
J D
JD
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-2465.
Illig
M
M
Romberger
D
D
Rennard
S I
SI
D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D062368:meta-Aminobenzoates
D062365:Aminobenzoates; D001549:Benzamides; D005353:Fibronectins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D062368:meta-Aminobenzoates; C025160:3-aminobenzamide; C044855:3-aminobenzoic acid