Disease relevance of TIMP1

• RESULTS: Genes found by RAP-PCR to undergo up-regulation in hypoxia included TIMP-1 and integrin-linked kinase [1].
• However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known [2].

Psychiatry related information on TIMP1

• The MMPI synthesized by retinol-treated EC was immunologically related to tissue inhibitor of metalloproteinases, type 1 (TIMP-1), and the MMPI produced by retinoic acid-treated cells was related to TIMP-2, as indicated by biosynthetic labeling and immunoprecipitation studies as well as Western blot analysis [3].

High impact information on TIMP1

• Tissue inhibitor of metalloproteinases 1 (TIMP-1) message was significantly enhanced by the cytokine in most instances, whereas TIMP-2 message was markedly decreased by IL-1beta in reoxygenated cultures [4].
• To prove that increased MMP or decreased TIMP expression could be a result of the autocrine action of VEGF on chondrocytes, we repeated the experiments in the presence of a specific inhibitor for the kinase activity of the VEGFR-2 [5].
• Sensitivity to known matrix metalloproteinase inhibitors as well as to the endogenous tissue inhibitor of metalloproteinases, TIMP-1, further support the notion that aggrecanase is a metalloproteinase potentially related to the ADAM family or MMP family of proteases previously implicated in the catabolism of the extracellular matrix [6].
• Retinoids modulate endothelial cell production of matrix-degrading proteases and tissue inhibitors of metalloproteinases (TIMP) [3].
• Hence, regulation of the MMP-9/TIMP balance failed to correlate with the migratory or invasive capacity [7].

Biological context of TIMP1

• Retinoids and TIMP1 prevent radiation-induced apoptosis of capillary endothelial cells [8].
• However, addition of both factors together revealed a striking synergistic effect causing upregulation of MMP-9 and downregulation of TIMPs, thereby increasing the net MMP-9/TIMP balance and the gelatinolytic capacity [7].
• Western blot analysis, anti-proteinase activities against metalloproteinases, and the nucleotide sequence of cDNA isolated from a lambda gt11 cDNA library of the bovine ovary by a polyclonal antibody against embryogenin-1 [9].
• Embryogenin-1 has a molecular weight of 31,100 (reduced) and has been identified as a bovine tissue inhibitor of metalloproteinase-1 by NH2-terminal amino acid sequence analysis [9].
• TIMP mRNA is only weakly expressed in follicular granulosa- and theca cells, whereas luteinization of the follicle is associated with an increase of expression [10].

Anatomical context of TIMP1

• High expression levels of MMP, TIMP, and PA family members seem to be a typical feature of the nonlactating mammary gland [11].
• Tissue inhibitor of metalloproteinases (TIMP-1) produced by granulosa and oviduct cells enhances in vitro development of bovine embryo [9].
• Trabecular cells would modify extracellular matrix in response to such mechanical stimuli as bending of trabecular meshwork or aqueous flow by the production of TIMP-1 and MMP-2 [12].
• Immunohistochemistry revealed that both TIMP-1 and -2 were localized to large luteal cells from all three ages of CL [13].
• In addition, senescent fibroblasts constitutively express a relatively small amount of TIMP which is not induced upon serum stimulation [14].

Associations of TIMP1 with chemical compounds

• The IL-1 decreased expression of TIMP-1 was further reduced by dexamethasone, which resulted in a significant loss of TIMP activity [15].
• RP 59794 blocks complex formation and can partially dissociate established TIMP: collagenase complexes [16].
• In conclusion, our data indicate that BOEC secrete TIMP-1 and this glycoprotein promotes the prehatched development of "HanWoo" embryos derived from in vitro-fertilization [17].
• When examined TIMP-1 secretion, fluorescent foci indicating the secretion of TIMP-1 were found after stained BOEC with fluorescein isothiocyanate [17].

Regulatory relationships of TIMP1

• Treating chondrocytes with IL-1 induced the expression of MMPs and downregulated TIMP-1 but stimulated both the expression of PAs and PAI-1 [18].
• Cyclic hydrostatic pressure downregulated the expression of MMP-13 and type I collagen and upregulated expression of TIMP-1 compared to the unloaded controls [19].
• These results suggest that IL-4 is able to specifically block cartilage collagen resorption by down-regulating the production of collagenase (MMP-1) and up-regulating TIMP-1 by chondrocytes within the cartilage [20].

Other interactions of TIMP1

• The stretched cells produced significantly larger amounts of metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) after 72 hours, compared with cells in nonstretched control [12].
• We have examined the regulation of the gelatinase/TIMP balance by transforming growth factor-beta1 (TGF-beta1) and phorbol myristate acetate (PMA) in bovine endothelial cells [7].
• Temporal and spatial expression of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2) in the bovine corpus luteum [13].
• This evidence indicates that fragments originating from TSP-1 switch the pro- or anti-angiogenic phenotype in endothelium by targeting MAPK cascades with opposite functions on MMP/TIMP balance [21].
• Within the protein coding region of the bovine StAR gene, there is a marked 124 base homology to the 5' non-coding region of another luteal transcript, TIMP-1, suggesting a possible common regulatory function for this sequence [22].

Analytical, diagnostic and therapeutic context of TIMP1

• Amino terminal sequence analysis for the first 22 amino acids of the purified inhibitor was also found to be identical to bovine TIMP-1 [23].
• The smaller ESA (embryogenin-1) in BGC-CM was purified to homogeneity, as a common activity in both CM by a combination of gel-permeation chromatography, ion-exchange chromatography, and reverse-phase HPLC [9].
• A cDNA library derived from poly(A+)RNA of bovine ovary was screened with a PCR fragment comprising the coding region of human tissue inhibitor of metalloproteinase inhibitor (TIMP) [10].
• Northern blotting revealed that the TIMP-1 transcript (0.9 kb) was expressed at a higher (p < 0.05) level in early and mid cycle CL than in the late stage [13].
• No effects on TIMP activity or TIMP-1 biosynthesis were observed after treatment of chondrocytes with PSGAG [18].

References