COLLAGEN BIOSYNTHESIS IN HUMAN ORAL SUBMUCOUS FIBROSIS FIBROBLAST-CULTURES

To investigate the mechanism of collagen accumulation in oral submucou s fibrosis (OSF) tissues, we examined the biosynthesis of collagen in fibroblast cultures established from OSF lesions. Fibroblasts obtained from four of ten OSF specimens showed more than a 1.5-fold increase i n the production of collagens compared with fibroblasts from age-, sex -, and passage-matched normal controls (p < 0.05). When the relative a mounts of collagen synthesis were estimated by SDS polyacrylamide,eel electrophoresis, it was found that both OSF and control cells produced about 85% type I collagen and 15% type III collagen. The ratio of alp ha 1(I) to alpha 2(I) chains was about 3:1 in OSF cells instead of the 2:1 expected for type I collagen. The excess alpha 1(I) chains could mean that collagen type I trimer was synthesized by the fibroblasts. T hese findings suggest that collagen overproduction and a reduced degra dation of the structure-stable collagen type I trimer synthesized by O SF fibroblasts might contribute to the accumulation of collagen in OSF lesions in vivo. The mechanism(s) of increased procollagen production were analyzed by Northern blot, slot blot, and Southern blot. The OSF fibroblast strains with elevated collagen production also contained h igher-than-normal levels of procollagen mRNA, and the ratios of alpha 1(I), alpha 2(I), and alpha 1(III) procollagen mRNAs were compatible w ith the results of corresponding procollagen alpha chains. The gene co py number of pro alpha 2(I) collagen gene in OSF fibroblasts was about 1.05. No gene amplification was found. These results indicate that ex pression of these procollagen genes in cultured fibroblasts is regulat ed at the transcriptional level.