Disease relevance of TIMP3

• Differentiation expression of TIMP3 in choriocarcinoma may have potential application in clinical diagnosis and patient treatment [1].
• These findings establish the potential of adenoviral gene delivery of TIMP3 as a therapeutic agent for selected lung cancers [2].
• RESULTS: Methylation frequencies of TIMP3 in the breast cancer samples were 20.81 % [3].
• CONCLUSION: The result demonstrated that hypermethylation of TIMP3 in IDC might be associated with high tumor grading and lymph nodes metastasis, and overexpression of ER, PR and c-erbB2, respectively [3].
• DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma [3].

Psychiatry related information on TIMP3

• Attention and memory for somatic symptom and IEI-trigger words was compared among participants with IEI (n = 54), somatoform disorders (SFD; n = 44) and control participants (n = 54) [4].

High impact information on TIMP3

• These data indicate that TIMP3 is a crucial innate negative regulator of TNF in both tissue homeostasis and tissue response to injury [5].
• In a liver regeneration model that requires TNF signaling, Timp3(-/-) mice succumbed to liver failure [5].
• Hepatocytes from Timp3(-/-) mice completed the cell cycle but then underwent cell death owing to sustained activation of TNF [5].
• The increase in TNF in Timp3(-/-) mice culminated in hepatic lymphocyte infiltration and necrosis, features that are also seen in chronic active hepatitis in humans [5].
• In a SFD family with a novel TIMP3 point mutation, we tested a hypothesis that their night blindness is due to a chronic deprivation of vitamin A at the level of the photoreceptors caused by a thickened membrane barrier between the photoreceptor layer and its blood supply [6].

Chemical compound and disease context of TIMP3

• Treatment with a demethylation drug, 5-aza-2'-deoxycytidine, in choriocarcinoma cell lines restored TIMP3 expression [1].
• Thus, high tumour levels of the matrix metalloproteinases inhibitor and pro-apoptotic factor TIMP-3 are associated with successful tamoxifen treatment of patients with breast cancer [7].
• These results suggest that an inverse expression pattern of ADAM-17/TACE and TIMP-3, and the regulation of ADAMs with DHT might play an important role in the pathogenesis of prostate cancer [8].

Biological context of TIMP3

• When microglia were activated, there was an upregulation of transcripts for nine metalloproteinases, and reduction of TIMP3 [9].
• The involvement of promoter methylation in suppression of TIMP3 expression in choriocarcinoma was examined using methylation-specific PCR (MSP) and demethylation treatment [1].
• OBJECTIVE: To assess the differential gene expression in neoplastic and normal trophoblastic cells and evaluate the effect of methylation on tissue inhibitor of metalloproteinase 3 (TIMP3) expression in choriocarcinoma (CCA) cells [1].
• Down-regulation of TIMP3 expression was confirmed in clinical specimens of choriocarcinoma and may play a role in its pathogenesis [1].
• A SpeI RFLP for E139X TIMP3 is described [10].

Anatomical context of TIMP3

• TIMP1, TIMP2, and TIMP3 were highly expressed in lung fibroblasts [11].
• A mutant TIMP-3 in which serine 181 was changed to a cysteine, found in Sorsby's fundus dystrophy, a hereditary macular degenerative disease, was also expressed in COS-7 cells [12].
• TIMP-3 mRNA was strongly expressed within the retinal pigment epithelial cell layer and also in the stroma of one membrane [13].
• CONCLUSIONS: TIMP-3 regulates the release of sVCAM-1 from cytokine-stimulated endothelial cells, which is mediated by ADAM17 [14].
• Most of the membranes also expressed TIMP-1 and TIMP-3 mRNA, and two of the membranes expressed TIMP-2 mRNA [13].

Associations of TIMP3 with chemical compounds

• Low levels of endogenous TIMP3 protein expression were elevated using the natural polysaccharide calcium pentosan polysulfate (CaPPs) in combination with the cytokine IL-1alpha [10].
• Because TIMP-3 is sequestered in the extracellular matrix, the presence of certain heparan sulfate proteoglycans could enhance its inhibitory capacity [15].
• Thus the functional domain arrangement of TIMP-3 is analogous to that seen in TIMP-1 and -2, namely that the NH2-terminal domain is responsible for MMP inhibition whereas the COOH-terminal domain is most important in mediating the specific functions of the molecule [12].
• The enhanced invasion capacity of MMP-13 expressing HT-1080 cells was dependent on MMP activity, as it was blocked by MMP inhibitor Batimastat (BB-94) and tissue inhibitor of metalloproteinases-3 (TIMP-3) [16].
• We have cloned and sequenced a third human TIMP (hTIMP-3) from phorbol ester-differentiated THP-1 cells stimulated with bacterial lipopolysaccharide [17].

Physical interactions of TIMP3

• We set out to delineate the basis for this specificity by examining the solvent accessibility of every epitope on the surface of a model of the truncated N-terminal domain form of TIMP-3 (N-TIMP-3) in a hypothetical complex with the crystal structure of TACE [18].
• Further studies of the features of TIMP-3 that determine specific binding to both ADAM and glycosaminoglycan are required in order to understand these unique properties [19].

Regulatory relationships of TIMP3

• The K562 cells expressed more TIMP-1 than the HL-60 cells and neither cell line expressed TIMP-3 [20].
• Elf3 upregulated the TIMP3 promoter, with Elf3a and -3b inducing an approximate sixfold increase in activity [21].
• Among the four variants of mammalian tissue inhibitor of metalloproteinases (TIMP-1 to -4), TACE is specifically inhibited by TIMP-3 [18].
• We showed that the cells' TIMP-3 expression is regulated in accord with that of MMP-9 [22].
• Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis [23].

Other interactions of TIMP3

• The exchange of portions of the gelatinase A hemopexin domain with that of stromelysin revealed that residues 568-631 of gelatinase A were required for rapid association with TIMP-3 [15].
• TIMP-1, TIMP-2, and TIMP-3 expression was low in all samples [24].
• In addition, a prolonged effect of acrolein may be mediated by altering MMP9 and TIMP3 transcription [25].
• In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA [26].
• Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum [27].

Analytical, diagnostic and therapeutic context of TIMP3

• Differential expression of a specific gene, TIMP3, was confirmed by immunohistochemistry using clinical specimens of choriocarcinoma and placenta [1].
• Immunoblotting detected protein expression from both wild-type and mutant alleles, S181C TIMP3 or E139X TIMP3 [10].
• By RT-PCR, TIMP-2 and TIMP-3 expression did not change with tumour grade [28].
• We analyzed the expression and role of these MMPs and their specific inhibitors TIMP-2 and TIMP-3 in human highly purified thyroid epithelial, C 643, HTh 74, SW 1736, and 8505 C thyroid carcinoma and thyroid-derived fibroblast cell cultures [29].
• This stimulatory effect of DBcAMP on TIMP-3 expression was confirmed at the mRNA and intracellular protein levels by Northern and Western blotting, respectively [30].

References