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Gene Review

TIMP1  -  TIMP metallopeptidase inhibitor 1

Ovis aries

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Disease relevance of TIMP-1


High impact information on TIMP-1


Biological context of TIMP-1

  • The 887-basepair cDNA obtained was 95%, 86%, and 77% identical to the reported nucleotide sequences of bovine, human, and mouse TIMP-1 cDNAs, respectively [3].
  • Concentrations of TIMP-1 mRNA in luteal tissue did not differ throughout the luteal phase (P = 0.07) [3].
  • We previously reported a decrease in luteal TIMP-1 within 15 min of prostaglandin F(2 alpha) (PGF(2 alpha))-induced luteolysis [4].
  • Expression of mRNA for TIMP-1 and TIMP-2 was examined by Northern analysis of endometrial RNA derived from steroid-treated ovariectomized ewes and from intact ewes during the estrous cycle and early pregnancy [5].
  • In experiment 1, we tested the effects of PGF(2alpha) administration (Day 10 postestrus; Day 0 = estrus) on luteal TIMP-1, -2, and -3 mRNA and protein expression [6].

Anatomical context of TIMP-1

  • However, TIMP-1 mRNA was localized predominantly to specific cells located in the connective tissue surrounding and within day 3 corpora lutea [3].
  • We investigated whether PGF(2alpha) also influenced the endogenous protein levels of tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, and matrix metalloproteinases, MMP-2 and MMP-9, all of which have been implicated in remodeling of the extracellular matrix (ECM) [7].
  • TIMP-1 immunoreactivity was observed within the granulosa cells of postsurge but not presurge follicles [8].
  • TIMP-1 was secreted by both epithelial and stromal cells in primary culture, and its identity was confirmed by Western analysis, while reverse zymography demonstrated TIMP-1 and TIMP-2 along with a putative ovine TIMP-3 in the culture medium from both cell types [5].
  • TIMP-1 immunoactivity was localized in large luteal cells, smooth muscle and endothelial cells, and in all antral follicles, including oocytes [9].

Associations of TIMP-1 with chemical compounds

  • Serum concentrations of progesterone and luteal concentrations of TIMP-1 mRNA and protein were similar at 0 and 6 h after PGF(2alpha) injection on Day 3 postestrus [6].
  • In situ hybridization for MCP-1 mRNA combined with immunocytochemical labeling of tissue inhibitor of metalloproteinase-1 (TIMP-1) in large luteal cells was used to determine whether the steroidogenic cells that have PGF2alpha receptors express MCP-1 mRNA in response to PGF2alpha [10].

Other interactions of TIMP-1

  • In parallel to the development of LVH at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3 [11].
  • In contrast to the rapid decrease in TIMP-1 and -2 levels, an increase in MMP-2 activity (165% of controls, P < 0.05) occurred at 8 h, which corresponded to the nadir in plasma progesterone [7].
  • Collagen I, III and IV, alpha-smooth muscle actin, MMP-1, 2 and 9, TIMP-1 and 2 and PAX2 protein were assessed using immunochemistry [12].
  • It has been suggested in postnatal animal studies that dysregulation of the RAS, and subsequent increased expression of TGF-beta1 and TIMP1, leads to changes in extracellular matrix composition [1].

Analytical, diagnostic and therapeutic context of TIMP-1


  1. Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney. Ayan, S., Roth, J.A., Freeman, M.R., Bride, S.H., Peters, C.A. Urology (2001) [Pubmed]
  2. Tissue inhibitor of metalloproteinases (TIMP) regulates extracellular type I collagen degradation by chondrocytes and endothelial cells. Gavrilovic, J., Hembry, R.M., Reynolds, J.J., Murphy, G. J. Cell. Sci. (1987) [Pubmed]
  3. Molecular cloning of an ovine ovarian tissue inhibitor of metalloproteinases: ontogeny of messenger ribonucleic acid expression and in situ localization within preovulatory follicles and luteal tissue. Smith, G.W., Goetz, T.L., Anthony, R.V., Smith, M.F. Endocrinology (1994) [Pubmed]
  4. Matrix metalloproteinase expression and activity following prostaglandin F(2 alpha)-induced luteolysis. Ricke, W.A., Smith, G.W., Smith, M.F. Biol. Reprod. (2002) [Pubmed]
  5. Tissue inhibitors of metalloproteinases in endometrium of ovariectomized steroid-treated ewes and during the estrous cycle and early pregnancy. Hampton, A.L., Butt, A.R., Riley, S.C., Salamonsen, L.A. Biol. Reprod. (1995) [Pubmed]
  6. Analysis of luteal tissue inhibitor of metalloproteinase-1, -2, and -3 during prostaglandin F(2alpha)-induced luteolysis. Ricke, W.A., Smith, G.W., McIntush, E.W., Smith, M.F. Biol. Reprod. (2002) [Pubmed]
  7. Dynamic in vivo changes in tissue inhibitors of metalloproteinases 1 and 2, and matrix metalloproteinases 2 and 9, during prostaglandin F(2alpha)-induced luteolysis in sheep. Towle, T.A., Tsang, P.C., Milvae, R.A., Newbury, M.K., McCracken, J.A. Biol. Reprod. (2002) [Pubmed]
  8. Immunolocalization of tissue inhibitor of metalloproteinases-1 within ovine periovulatory follicular and luteal tissues. McIntush, E.W., Pletz, J.D., Smith, G.D., Long, D.K., Sawyer, H.R., Smith, M.F. Biol. Reprod. (1996) [Pubmed]
  9. Effect of immunization against the amino-terminal peptide (alpha N) of the alpha 43-subunit of inhibin on follicular atresia and expression of tissue inhibitor of matrix metalloproteinase (TIMP-1) in ovarian follicles of sheep. Dhar, A., Salamonsen, L.A., Doughton, B.W., Brown, R.W., Findlay, J.K. J. Reprod. Fertil. (1998) [Pubmed]
  10. Messenger ribonucleic acid encoding monocyte chemoattractant protein-1 is expressed by the ovine corpus luteum in response to prostaglandin F2alpha. Haworth, J.D., Rollyson, M.K., Silva, P., McIntush, E.W., Niswender, G.D. Biol. Reprod. (1998) [Pubmed]
  11. Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression. Walther, T., Schubert, A., Falk, V., Binner, C., Kanev, A., Bleiziffer, S., Walther, C., Doll, N., Autschbach, R., Mohr, F.W. Circulation (2001) [Pubmed]
  12. Complete unilateral ureteral obstruction in the fetal lamb. Part II: Long-term outcomes of renal tissue development. Mure, P.Y., Gelas, T., Dijoud, F., Guerret, S., Benchaib, M., Hartmann, D.J., Mouriquand, P. J. Urol. (2006) [Pubmed]
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