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Gene Review

TIMP1  -  TIMP metallopeptidase inhibitor 1

Canis lupus familiaris

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Disease relevance of TIMP1


High impact information on TIMP1

  • Our findings suggest that lymphocytes infiltrating the ischemic and reperfused myocardium express IL-10 and may have a significant role in healing by modulating mononuclear cell phenotype and inducing TIMP-1 expression [5].
  • In OA cartilage, PA was present only at the superficial level in chondrocytes and in cartilage matrix, whereas TIMP was present in chondrocyte lacunae throughout the full thickness of the cartilage [6].
  • Although the TIMP level was increased in the OA synovium, it was found only in trace amounts in cartilage [6].
  • MMP-1, MMP-2, TIMP-1, TIMP-2, and urokinase-type PA levels in the distribution of the LAD were higher in the laser group than in the control or sham group [7].
  • Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs [8].

Biological context of TIMP1

  • The canine TIMP-1 spans 3.5kb and is interrupted by five introns with sizes comparable to those observed in the human and mouse homologues of the gene [1].
  • The proximal promoter region of canine TIMP-1 contains sequence motifs shown to have regulatory significance in transcription of human TIMP-1 [1].

Anatomical context of TIMP1


Associations of TIMP1 with chemical compounds

  • Active and total neutral metalloproteinase, tissue inhibitor of metalloproteinases (TIMP), total collagenase, uronate and hydroxyproline contents were all near normal in the IGF-1/PPS group [10].
  • OBJECTIVE: To explore the levels of matrix metalloprotease-3 (MMP-3), tissue inhibitor of metalloproteases-1 (TIMP-1), 5D4 keratan sulfate, and two 3B3 chondroitin-sulfate epitopes in several canine osteoarthritic and inflammatory arthropathies [11].
  • Whether the abnormal changes of protease-TIMP balance in knee cartilage can be retarded prophylactically by concurrent treatment with pentosan polysulfate and insulin like growth factor 1 remains uncertain [12].

Analytical, diagnostic and therapeutic context of TIMP1

  • Compared with the control group, MMP-9 was significantly higher (0.217 +/- 2.16 E-02 vs. 0.314 +/- 5.263 E-02; p < 0.001), while TIMP-1 was decreased (0.230 +/- 8.944 E-02 vs. 0.120 +/- 9.258 E-03; p < 0.001) [2].
  • The relative abundance of matrix metalloproteinase (MMP)-9 and TIMP-1 was studied by immunoblotting [2].
  • Immobilisation decreased the joint lavage fluid levels of IL1alpha (p<0.05), TIMP (p< 0.05), and the concentration of CS down to 38% (p<0.05) in comparison with untreated litter mates with normal weight bearing [8].
  • The molar ratio of MMP-3 to TIMP-1 was higher (p = 0.001) in group II than in group I. The changes observed in the concentration of synovial fluid markers in this slowly progressive canine OA model suggest that activation of an inflammation-related process occurs at an early stage of the OA disease induced by unilateral tibial valgus osteotomy [4].
  • Synovial fluid samples of 17 dogs with CRA were analysed for MMP-3 and TIMP-1 by two canine sandwich ELISA (enzyme-linked immunosorbent assay) systems [3].


  1. TIMP-1 expression is increased in X-linked progressive retinal atrophy despite its exclusion as a candidate gene. Zeiss, C.J., Acland, G.M., Aguirre, G.D., RayK, n.u.l.l. Gene (1998) [Pubmed]
  2. Changes in metalloproteinase and tissue inhibitor of metalloproteinase during tachycardia-induced cardiomyopathy by rapid atrial pacing in dogs. Zhong, J.Q., Zhang, W., Li, Y., Zhong, M., Li, D., Zhang, C., Zhang, Y. Cardiology (2006) [Pubmed]
  3. Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis. Hegemann, N., Wondimu, A., Ullrich, K., Schmidt, M.F. Vet. Immunol. Immunopathol. (2003) [Pubmed]
  4. Elevated levels of synovial fluid PLA2, stromelysin (MMP-3) and TIMP in early osteoarthrosis after tibial valgus osteotomy in young beagle dogs. Panula, H.E., Lohmander, L.S., Rönkkö, S., Agren, U., Helminen, H.J., Kiviranta, I. Acta orthopaedica Scandinavica. (1998) [Pubmed]
  5. IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. Frangogiannis, N.G., Mendoza, L.H., Lindsey, M.L., Ballantyne, C.M., Michael, L.H., Smith, C.W., Entman, M.L. J. Immunol. (2000) [Pubmed]
  6. Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. Pelletier, J.P., Mineau, F., Faure, M.P., Martel-Pelletier, J. Arthritis Rheum. (1990) [Pubmed]
  7. Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs. Li, W., Tanaka, K., Chiba, Y., Kimura, T., Morioka, K., Uesaka, T., Ihaya, A., Sasaki, M., Tsuda, T., Yamada, N. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  8. Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs. Haapala, J., Arokoski, J.P., Rönkkö, S., Agren, U., Kosma, V.M., Lohmander, L.S., Tammi, M., Helminen, H.J., Kiviranta, I. Ann. Rheum. Dis. (2001) [Pubmed]
  9. Immunological and inflammatory characterisation of three canine cell lines: K1, K6 and DH82. Barnes, A., Bee, A., Bell, S., Gilmore, W., Mee, A., Morris, R., Carter, S.D. Vet. Immunol. Immunopathol. (2000) [Pubmed]
  10. Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate. Rogachefsky, R.A., Dean, D.D., Howell, D.S., Altman, R.D. Osteoarthr. Cartil. (1993) [Pubmed]
  11. Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders. Hegemann, N., Kohn, B., Brunnberg, L., Schmidt, M.F. Osteoarthr. Cartil. (2002) [Pubmed]
  12. Cartilage metalloproteases in disuse atrophy. Grumbles, R.M., Howell, D.S., Howard, G.A., Roos, B.A., Setton, L.A., Mow, V.C., Ratcliffe, A., Muller, F.J., Altman, R.D. The Journal of rheumatology. Supplement. (1995) [Pubmed]
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