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.

[1]  V. Stanescu The small proteoglycans of cartilage matrix. , 1990, Seminars in arthritis and rheumatism.

[2]  E. Ginns,et al.  Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis , 1998, The Journal of cell biology.

[3]  X. Chen,et al.  Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence. , 1994, Genomics.

[4]  H. Larjava,et al.  Differential regulation of decorin and biglycan gene expression by dexamethasone and retinoic acid in cultured human skin fibroblasts. , 1995, The Journal of investigative dermatology.

[5]  Edward L. Schneider,et al.  Handbook of the Biology of Aging , 1990 .

[6]  C. Moroni,et al.  Improved efficiency for single-sided PCR by creating a reusable pool of first-strand cDNA coupled to a solid phase. , 1991, Nucleic acids research.

[7]  D. Heinegård,et al.  Binding of fibromodulin and decorin to separate sites on fibrillar collagens. , 1993, The Journal of biological chemistry.

[8]  D. Heinegård,et al.  Structure and deduced amino acid sequence of the human fibromodulin gene. , 1993, Biochimica et biophysica acta.

[9]  D. Heinegård,et al.  Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. , 1989, The Journal of biological chemistry.

[10]  H. Jasin,et al.  Inhibition of human fibroblast adhesion by cartilage surface proteoglycans. , 1994, Arthritis and rheumatism.

[11]  H. Huland,et al.  Long-term monitoring of 486P 3/12 antigen pattern (quantitative immunocytology) before, during, and after mitomycin C prophylaxis in patients with superficial bladder cancer. , 1995, Urology.

[12]  J. Petri,et al.  Molecular analysis of different phases in human wound healing , 1997, Experimental dermatology.

[13]  P. Newman,et al.  Enzymatic amplification of specific cDNA inserts from λgt11 libraries , 1988 .

[14]  L. Sakai,et al.  Elastin-associated microfibrils (10 nm) in a three-dimensional fibroblast culture. , 1991, The Journal of investigative dermatology.

[15]  Ignacio R. Rodriguez,et al.  A novel method for the isolation of tissue-specific genes , 1992, Nucleic Acids Res..

[16]  B. Coulomb,et al.  Glycosaminoglycans modulate cell-matrix interactions of human fibroblasts and endothelial cells in vitro. , 1996, Journal of cell science.

[17]  F. Reinholt,et al.  Fibromodulin distribution and association with collagen. , 1994, Matrix biology : journal of the International Society for Matrix Biology.

[18]  Renato V. Iozzo,et al.  Targeted Disruption of Decorin Leads to Abnormal Collagen Fibril Morphology and Skin Fragility , 1997, Journal of Cell Biology.

[19]  M. Young,et al.  Human biglycan gene. Putative promoter, intron-exon junctions, and chromosomal localization. , 1991, The Journal of biological chemistry.

[20]  K. Dittmann,et al.  Selective enrichment and biochemical characterization of seven human skin fibroblasts cell types in vitro. , 1989, Experimental cell research.

[21]  L. Hayflick,et al.  The serial cultivation of human diploid cell strains. , 1961, Experimental cell research.

[22]  Terry Magnuson,et al.  Lumican Regulates Collagen Fibril Assembly: Skin Fragility and Corneal Opacity in the Absence of Lumican , 1998, The Journal of cell biology.

[23]  J. Scott Proteodermatan and proteokeratan sulfate (decorin, lumican/fibromodulin) proteins are horseshoe shaped. Implications for their interactions with collagen. , 1996, Biochemistry.