Control of Procollagen Gene Transcription and Prolyl Hydroxylase Activity by Poly(ADP-Ribose)

Abstract

The synthesis of collagen increases during induced injury, growth and wound healing. There is an emerging consensus that collagen synthesis is controlled at the level of collagen gene transcription. The synthesis of specific collagen types in keloids (Bauer et al, 1986), virus transformed fibroblasts (Adams et al, 1982; Parker et al, 1979) and transforming growth factor-ß (TGF-ß) or interleukin-1 (IL-1) treated fibroblasts (Ignotz et al, 1987; Postlethwaite et al, 1988) is accompanied by an increase in the levels of the respective procollagen mRNAs. However, molecular events leading to this stimulation is not clear. Poly(ADPribose) is closely associated with the differentiation of several eukaryotic cells (Farzaneh et al, 1982; Ohashi et al, 1985) and is also implicated in the expression of individual genes (Kun et al, 1986; Poirer et al, 1982). (Tanuma et al, 1983) showed a clear relationship between ADP-ribosylation of HMG 14/HMG 17 and glucocorticoid regulated expression of MMTV gene. The use of 3-aminobenzamide (3-AB), lowered poly(ADP-ribose) levels on these nuclear proteins and enhanced the level of MMTV mRNA. Similarly, the expressions of c-myc and c-fos proto-oncogenes were stimulated by the treatment of fibroblasts with 3-methoxybenzamide (McNerney et al, 1987). Earlier, we found that exposure of fibroblasts to 20 mM lactate lowered [NAD+], total ADP-ribosylation and activated prolyl hydroxylase causing increased collagen synthesis (Hussain et al, 1989).