PLATELET-DERIVED-GROWTH-FACTORS-AA AND PLATELET-DERIVED-GROWTH-FACTORS-BB REGULATE COLLAGEN AND COLLAGENASE GENE-EXPRESSION DIFFERENTIALLY IN HUMAN FIBROBLASTS

Platelet-derived growth factor (PDGF) is a mitogen associated with tis sue repair, a process involving collagen synthesis and remodelling by interstitial collagenase. This study examines and compares the regulat ion of interstitial collagenase and collagen gene expression by PDGF-A A and -BB in human fibroblasts. Time-course analysis showed that neith er PDGF-AA or -BB had a consistent effect on the expression of pro-alp ha 1(I) or pro-alpha 2(I) type-I collagen genes. In contrast, intersti tial collagenase gene expression was found to be consistently up-regul ated severalfold by PDGF-BB. Enhanced expression of the collagenase ge ne was not apparently due to up-regulation of its promoter activity in human dermal fibroblasts, as indicated by transient and stable transf ection experiments. Unlike PDGF-BB, PDGF-AA did not alter collagenase mRNA levels under low-serum culture conditions. Thus, the biological a ctivities of the PDGF homodimers are different, with PDGF-BB being cle arly more potent than PDGF-AA in its regulation of collagenase gene ex pression.