HUMAN GRANULATION-TISSUE FIBROBLASTS SHOW ENHANCED PROTEOGLYCAN GENE-EXPRESSION AND ALTERED RESPONSE TO TGF-BETA-1

Granulation-tissue fibroblasts are phenotypically unique cells that pl ay an important role in wound repair and the development of chronic in flammatory lesions in connective tissue. In the present study, we comp ared proteoglycan, type I, and type III procollagen gene expression by granulation-tissue fibroblasts from wound and chronically inflamed ti ssues with normal gingival fibroblasts. We also analyzed the effect of TGF-beta 1 on proteoglycan mRNA levels and macromolecule production b y these cells. One granulation-tissue fibroblast strain that was compo sed exclusively of alpha-smooth-muscle actin-positive cells (myofibrob lasts) expressed strongly elevated basal levels of biglycan, fibromodu lin, and versican (the large chondroitin sulphate proteoglycan), as we ll as type I and III procollagen mRNA. TGF-beta 1 enhanced more potent ly the expression of types I and he procollagen, biglycan, and versica n mRNA by these cells as compared with normal fibroblasts. Other granu lation-tissue fibroblast strains, in which about half of the cells exp ressed alpha-smooth-muscle actin, also showed enhanced proteoglycan an d types I and III procollagen expression as compared with normal fibro blasts. These results suggest that alterations in matrix composition d uring inflammation and wound healing are regulated partly by altered p henotypes of the cells that produce the matrix, and partly by altered responses of these cells to TGF-beta 1.