Human Granulation-tissue Fibroblasts Show Enhanced Proteoglycan Gene Expression and Altered Response to TGF-β1

Abstract

Granulation-tissue fibroblasts are phenotypically unique cells that play an important role in wound repair and the development of chronic inflammatory lesions in connective tissue. In the present study, we compared proteoglycan, type I, and type III procollagen gene expression by granulation-tissue fibroblasts from wound and chronically inflamed tissues with normal gingival fibroblasts. We also analyzed the effect of TGF-β1 on proteoglycan mRNA levels and macromolecule production by these cells. One granulation-tissue fibroblast strain that was composed exclusively of a-smooth-muscle actin-positive cells (myofibroblasts) expressed strongly elevated basal levels of biglycan, fibromodulin, and versican (the large chondroitin sulphate proteoglycan), as well as type I and III procollagen mRNA. TGF-β1 enhanced more potently the expression of types I and III procollagen, biglycan, and versican mRNA by these cells as compared with normal fibroblasts. Other granulation-tissue fibroblast strains, in which about half of the cells expressed a-smooth-muscle actin, also showed enhanced proteoglycan and types I and III procollagen expression as compared with normal fibroblasts. These results suggest that alterations in matrix composition during inflammation and wound healing are regulated partly by altered phenotypes of the cells that produce the matrix, and partly by altered responses of these cells to TGF-β1.