Activation of tissue inhibitor of metalloproteinases-3 (TIMP-3) mRNA expression in scleroderma skin fibroblasts

被引:55
作者
Mattila, L
Airola, K
Ahonen, M
Hietarinta, M
Black, C
Saarialho-Kere, U
Kähäri, VM
机构
[1] Univ Turku, MediCity Res Lab, FIN-20520 Turku, Finland
[2] Univ Turku, Dept Biochem Med, FIN-20520 Turku, Finland
[3] Turku Univ, Cent Hosp, Dept Dermatol, Turku, Finland
[4] Turku Univ, Cent Hosp, Dept Internal Med, Turku, Finland
[5] Univ Helsinki, Cent Hosp, Dept Dermatol, FIN-00170 Helsinki, Finland
[6] Royal Free Hosp, Rheumatol Unit, London NW3 2QG, England
基金
芬兰科学院;
关键词
fibrosis; matrix metalloproteinase;
D O I
10.1046/j.1523-1747.1998.00138.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Excessive accumulation of fibrillar collagens is a hallmark of the cutaneous fibrosis in both systemic and localized scleroderma. Turnover of the collagenous extracellular matrix is dependent on the balance between collagenolytic matrix metalloproteinases and their specific inhibitors. We have examined the expression of the novel, matrix associated tissue inhibitor of metalloproteinases-3 (TIMP-3) in normal and scleroderma skin fibroblasts in culture and in vivo. The levels of TIMP-3 mRNA were elevated up to 2.5-fold in five of seven systemic sclerosis fibroblast strains, whereas TIMP-1 mRNA expression was elevated up to 1.8-fold in two and TIMP-2 mRNA expression up to 1.8-fold in two systemic sclerosis strains. Using irt situ hybridization, TIMP-3 mRNA was detected in seven of 12 localized scleroderma skin samples, specifically in fibroblasts within fibrotic collagen fibers or in the vicinity of inflammatory cells. TIMP-1 mRNA was detected in three of eight scleroderma skin samples in fibroblasts adjacent to inflammatory cells. The expression of TIMP-3 mRNA by systemic sclerosis and normal skin fibroblasts was enhanced to a similar extent (by 8.6- and 8.1-fold, respectively) by transforming growth factor-beta, and suppressed down to 34 and 54%, respectively, by tumor necrosis factor-alpha. Specific activation of TIMP-3 gene expression in scleroderma skill fibroblasts in culture and itt vivo suggests a role for TIMP-3 in the pathogenesis of dermal fibrosis via inhibition of turnover of fibrotic dermal extracellular matrix, possibly due to upregulation of TIMP-3 expression by transforming growth factor-beta.
引用
收藏
页码:416 / 421
页数:6
相关论文
共 56 条
  • [1] Human TIMP-3 is expressed during fetal development, hair growth cycle, and cancer progression
    Airola, K
    Ahonen, M
    Johansson, N
    Heikkilä, P
    Kere, J
    Kähäri, VM
    Saarialho-Kere, UK
    [J]. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1998, 46 (04) : 437 - 447
  • [2] PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC-SCLEROSIS (SCLERODERMA)
    不详
    [J]. ARTHRITIS AND RHEUMATISM, 1980, 23 (05): : 581 - 590
  • [3] CLONING OF THE CDNA-ENCODING HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES-3 (TIMP-3) AND MAPPING OF THE TIMP3 GENE TO CHROMOSOME-22
    APTE, SS
    MATTEI, MG
    OLSEN, BR
    [J]. GENOMICS, 1994, 19 (01) : 86 - 90
  • [4] THE GENE STRUCTURE OF TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP)-3 AND ITS INHIBITORY ACTIVITIES DEFINE THE DISTINCT TIMP GENE FAMILY
    APTE, SS
    OLSEN, BR
    MURPHY, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (24) : 14313 - 14318
  • [5] DISSOCIATION OF TNF-ALPHA CYTOTOXIC AND PROINFLAMMATORY ACTIVITIES BY P55 RECEPTOR-SELECTIVE AND P75 RECEPTOR-SELECTIVE TNF-ALPHA MUTANTS
    BARBARA, JAJ
    SMITH, WB
    GAMBLE, JR
    VANOSTADE, X
    VANDENABEELE, P
    TAVERNIER, J
    FIERS, W
    VADAS, MA
    LOPEZ, AF
    [J]. EMBO JOURNAL, 1994, 13 (04) : 843 - 850
  • [6] PRIMARY STRUCTURE AND CDNA CLONING OF HUMAN FIBROBLAST COLLAGENASE INHIBITOR
    CARMICHAEL, DF
    SOMMER, A
    THOMPSON, RC
    ANDERSON, DC
    SMITH, CG
    WELGUS, HG
    STRICKLIN, GP
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (08) : 2407 - 2411
  • [7] CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
  • [8] VARIOUS RAT ADULT TISSUES EXPRESS ONLY ONE MAJOR MESSENGER-RNA SPECIES FROM THE GLYCERALDEHYDE-3-PHOSPHATE-DEHYDROGENASE MULTIGENIC FAMILY
    FORT, P
    MARTY, L
    PIECHACZYK, M
    ELSABROUTY, S
    DANI, C
    JEANTEUR, P
    BLANCHARD, JM
    [J]. NUCLEIC ACIDS RESEARCH, 1985, 13 (05) : 1431 - 1442
  • [9] GHARIOS GB, 1994, CLIN CHIM ACTA, V231, P69
  • [10] GOLDBERG GI, 1986, J BIOL CHEM, V261, P6600