The small proteoglycan fibromodulin is expressed in mitotic, but not in postmitotic fibroblasts

The small proteoglycan fibromodulin is involved in a variety of adhesion processes of connective tissue, binds to collagen and seems to influence fibrillogenesis by regulating collagen fibril spacing and thickness. Using subtractive hybridisation and Northern blotting, we found expression of the fibromodulin gene only in mitotic but not in mitomycinC-induced postmitotic fibroblasts. Furthermore, we could show that in skin only fibroblasts but not endothelial cells and keratinocytes express fibromodulin. With age the thickness of collagen fibrils increases as well as the occurrence of postmitotic fibroblasts. We could show with different chemotaxis and similar collagen gel contraction experiments further physiological differences between mitotic and postmitotic fibroblasts. This is the first report showing the switch of mitotic to postmitotic fibroblasts at the molecular level. Therefore, fibromodulin provides a specific marker for mitotic versus postmitotic fibroblasts and could indicate cell ageing. Mitomycin C is therapeutically used in bladder carcinoma and could thus induce premature ageing of fibroblasts.