Spontaneous expression of immediately-early response genes c-fos and egr-1 in collagenase-producing rheumatoid synovial fibroblasts

SummaryIn view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could be detected in cytoplasmic extracts of collagenase-expressing synovial fibroblast-like cells when compared to equivalent RNA amounts isolated from control fibroblasts. Utilizing immunocytochemistry, immunoreactivity for c-fos oncoprotein was found in 13 of 19 joint specimens obtained from patients with active RA. These oncoprotein data were positively correlated to the collagenase expression in the same specimens. Moreover, immunohistochemical analysis confirmed the localization of both oncoprotein c-fos and fibroblast-type collagenase within synovial fibroblast-like cells attached to bone erosions.

[1]  K. Nishikura,et al.  Antisense RNA of proto-oncogene c-fos blocks renewed growth of quiescent 3T3 cells. , 1987, Molecular and cellular biology.

[2]  H. Birkedal‐Hansen,et al.  Expression of collagenase and potential transcriptional factors in the MRL/l mouse arthropathy. , 1992, Seminars in arthritis and rheumatism.

[3]  T. Curran,et al.  c-fos protein can induce cellular transformation: A novel mechanism of activation of a cellular oncogene , 1984, Cell.

[4]  H. Mitsuya,et al.  Expression of a zinc finger gene in HTLV-I- and HTLV-II-transformed cells. , 1990, Science.

[5]  D. Woolley,et al.  Collagenase at sites of cartilage erosion in the rheumatoid joint. , 1977, Arthritis and rheumatism.

[6]  H. Birkedal‐Hansen.  From tadpole collagenase to a family of matrix metalloproteinases. , 1988, Journal of oral pathology.

[7]  B. Hogan,et al.  Growth factor-regulated proteases and extracellular matrix remodeling during mammalian development. , 1990, Current topics in developmental biology.

[8]  S. Gay,et al.  Etiopathogenesis of rheumatoid arthritis-like disease in MRL/1 mice: II. Ultrastructural basis of joint destruction. , 1988, The Journal of rheumatology.

[9]  Eileen D. Adamson,et al.  A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization , 1988, Cell.

[10]  B. White,et al.  Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. , 1982, The Journal of biological chemistry.

[11]  I. Verma,et al.  Nuclear proto-oncogenes fos and jun. , 1990, Annual review of cell biology.

[12]  J. Mcghee,et al.  Expression of the collagenolytic and Ras-induced cysteine proteinase cathepsin L and proliferation-associated oncogenes in synovial cells of MRL/I mice and patients with rheumatoid arthritis. , 1990, Matrix.

[13]  G. Vaes,et al.  Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. , 1977, The Biochemical journal.

[14]  C. Overall,et al.  Concanavalin A produces a matrix-degradative phenotype in human fibroblasts. Induction and endogenous activation of collagenase, 72-kDa gelatinase, and Pump-1 is accompanied by the suppression of the tissue inhibitor of matrix metalloproteinases. , 1990, The Journal of biological chemistry.

[15]  V. Sukhatme,et al.  A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens. , 1987, Oncogene research.

[16]  L. Matrisian,et al.  Growth factors regulate transin gene expression by c-fos-dependent and c-fos-independent pathways. , 1988, Science.

[17]  E. Closs,et al.  c-fos expression precedes osteogenic differentiation of cartilage cells in vitro , 1990, The Journal of cell biology.

[18]  J. Milbrandt,et al.  A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. , 1987, Science.

[19]  A. Eisen,et al.  Human skin fibroblast procollagenase: mechanisms of activation by organomercurials and trypsin. , 1983, Biochemistry.

[20]  V. Sukhatme,et al.  Early transcriptional events in cell growth: the Egr family. , 1990, Journal of the American Society of Nephrology : JASN.

[21]  Michael E. Greenberg,et al.  Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene , 1984, Nature.

[22]  P. Lemaire,et al.  Two mouse genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Gay,et al.  Cellular basis and oncogene expression of rheumatoid joint destruction , 2004, Rheumatology International.

[24]  C. Brinckerhoff,et al.  Heat shock of rabbit synovial fibroblasts increases expression of mRNAs for two metalloproteinases, collagenase and stromelysin , 1989, The Journal of cell biology.

[25]  V. Sukhatme,et al.  5' flanking sequence and genomic structure of Egr-1, a murine mitogen inducible zinc finger encoding gene. , 1988, Nucleic acids research.

[26]  H. Birkedal‐Hansen,et al.  Monoclonal antibodies to human fibroblast procollagenase. Inhibition of enzymatic activity, affinity purification of the enzyme, and evidence for clustering of epitopes in the NH2-terminal end of the activated enzyme. , 1988, Biochemistry.

[27]  L. Lau,et al.  A gene activated in mouse 3T3 cells by serum growth factors encodes a protein with "zinc finger" sequences. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[28]  H. Fassbender,et al.  Histomorphological basis of articular cartilage destruction in rheumatoid arthritis. , 1983, Collagen and related research.

[29]  M. Stephenson,et al.  Mechanisms of Matrix Degradation in Rheumatoid Arthritis a , 1990, Annals of the New York Academy of Sciences.

[30]  H R Herschman,et al.  Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. , 1987, Oncogene.

[31]  K. Alitalo,et al.  Enhanced expression of TGF-beta and c-fos mRNAs in the growth plates of developing human long bones. , 1988, Development.

[32]  L. Moreland,et al.  Virus-like particles in synovial fluids from patients with rheumatoid arthritis. , 1993, British journal of rheumatology.

[33]  P. Herrlich,et al.  Comparison of human stromelysin and collagenase by cloning and sequence analysis. , 1986, The Biochemical journal.

[34]  K. Riabowol,et al.  Microinjection of fos-specific antibodies blocks DNA synthesis in fibroblast cells , 1988, Molecular and cellular biology.

[35]  M. de Silva,et al.  Identification of plasma kallikrein as an activator of latent collagenase in rheumatoid synovial fluid. , 1982, Biochimica et biophysica acta.

[36]  V. Sukhatme,et al.  cDNA sequence of the human cellular early growth response gene Egr-1. , 1990, Nucleic acids research.

[37]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[38]  H. Thoenen,et al.  The role of nerve growth factor (NGF) and related factors for the survival of peripheral neurons. , 1981, Advances in biochemical psychopharmacology.

[39]  A. McMahon,et al.  Developmental expression of the putative transcription factor Egr-1 suggests that Egr-1 and c-fos are coregulated in some tissues. , 1990, Development.

[40]  A. Schönthal,et al.  Requirement for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters , 1988, Cell.

[41]  P. Lemaire,et al.  Structure, chromosome mapping and regulation of the mouse zinc-finger gene Krox-24; evidence for a common regulatory pathway for immediate-early serum-response genes. , 1989, Gene.

[42]  Z. Werb,et al.  Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression , 1989, The Journal of cell biology.