Disease relevance of Timp2

• We investigate the effect of modified synthetic small interfering RNA (siRNA) targeting TIMP-2 in rat model of liver fibrosis [1].
• Furthermore, portal hypertension was also ameliorated after treatment with siRNA targeting TIMP-2 [1].
• CONCLUSIONS: The changes of MMP-2 and TIMP-2 expressions in kidney tissues of diabetes rats may contribute to the occurrence and progression of diabetic nephropathy [2].
• CONCLUSION: Our findings indicate that long-term increases of gelatinolytic activity of active MMP-2 cause continuous disorganization of type IV collagen in basement membranes during progressive atrophy of pancreatic gland in oleic acid-induced pancreatitis, and that MT1-MMP and TIMP-2 work as activating factors during proMMP-2 activation [3].
• Ribonuclease protection analysis of liver RNA extracted at each recovery time point demonstrated a rapid decrease in expression of the collagenase inhibitors TIMP-1 and TIMP-2, whereas collagenase mRNA expression remained at levels comparable to peak fibrosis [4].

High impact information on Timp2

• Growth activity was unlikely due to TIMP-2 inhibition of matrix metalloproteinases because ilomastat, a synthetic inhibitor of these enzymes, had no mesenchymal growth action [5].
• Hence, the mesenchyme synchronizes its own growth with ureteric morphogenesis by stimulating the secretion of TIMP-2 from the ureteric bud [5].
• During the first month after injury, we found that the expression of two proteinase inhibitors (plasminogen activator inhibitor type 1 [PAI-1] and tissue inhibitor of metalloproteinases-2 [TIMP-2]) was modulated [6].
• TIMP-2 protein was increased in the intima compared with the media and adventitia at day 7 after injury [6].
• The levels of collagen, collagen alpha1(I) gene expression, TIMP-2 content, and smooth muscle actin-positive cells were as in the control rats [7].

Chemical compound and disease context of Timp2

• Benazepril could exert protective effects on diabetic nephropathy, owing to the upregulation of MMP-2 and downregulation of TIMP-2 expressions, which further inhibits the excessive deposition of extracellular matrix in the glomerulus [2].
• Here we report that the expression of TIMP-2, a matrix metalloproteinase inhibitor, is up-regulated by signals that control proliferation (bFGF and EGF) and differentiation (retinoic acid and NGF) in neural progenitor and neuroblastoma cell lines [8].
• Temporal studies of progressive rat liver fibrosis caused by bile duct ligation or by carbon tetrachloride, indicate an important role for increased TIMP-1 and TIMP-2 expression in pathogenesis [9].

Biological context of Timp2

• The gene expression of MMP-2 and TIMP-2 was measured by reverse transcription polymerase chain reaction (RT-PCR) [2].
• The expression levels of MMP-9 increased 18 h and 36 h after parturition as determined by gelatin zymography including the expression levels of TIMP-1 and TIMP-2 [10].
• PURPOSE: To determine the expression of gelatinases A and B and the localization of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of corneal wound healing in rats [11].
• The localization pattern of TIMP-2 mRNA was unchanged through the latter stages of pseudopregnancy [12].
• Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues [13].

Anatomical context of Timp2

• However, AII-treated mesangial cells did show an increase in the amount of tissue inhibitor of metalloproteinase-2 (Timp2) immunoreactive protein secreted into the medium [14].
• Rats administered siRNA targeting TIMP-2 showed promotion of ECM degradation, reduction in activated hepatic stellate cells and enhancement of hepatocyte regeneration [1].
• At 12 h after hCG, luteinizing granulosa cells expressed TIMP-1 and TIMP-3 mRNA, but TIMP-2 mRNA was at levels equivalent to the background [15].
• There were no significant differences in tissue inhibitor of metalloproteinase (TIMP-1 or TIMP-2) activity by reverse zymography in small renal arteries [16].
• In situ hybridization showed that on day 1-4 of pregnancy, both MMP-2 and TIMP-2 mRNAs were evidently localized in the basal stromal cells [17].

Associations of Timp2 with chemical compounds

• To test the role of extracellular matrix degradation in hyperoxic damage, we analyzed the expression of gelatinases A and B and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in rats exposed to 85% O2 [18].
• The effect of ethanol and acetaldehyde on MMP2 and TIMP2 secretion was also assessed by this method [19].
• Membrane-type 1 MMP (MT1-MMP) mRNA was upregulated early and tissue inhibitor 2 of MMP (TIMP-2) mRNA later during wound healing [20].
• Live labeling experiments demonstrate TIMP-2 expression only on alpha(3) integrin-positive cells [8].
• Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity [21].

Regulatory relationships of Timp2

• Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1 [21].
• Following FTS treatment, the MMP-2 and MMP-9-induced collagenolytic activity and TIMP-2 expression, were increased in FTS-compared to PBS-treated rats [22].
• Investigation of this layer in every resorption area by gelatin histozymography and TIMP-2 histochemistry demonstrates the presence of an MMP whose histozymographic activity is inhibited by such a low dose of the inhibitor CT1746 as to identify it as gelatinase A or B [23].

Other interactions of Timp2

• TIMP-1 and TIMP-2 were constitutively expressed, and only TIMP-1 displayed a moderate increase with hyperoxia [18].
• TIMP-2 and TIMP-3 transcripts become detectable on day 10 and remained stable afterwards [24].
• Gelatinase A (MMP-2) was maximally increased at 5 days, and TIMP-2 was highest at 5 days [25].
• MMP-13 active form was elevated during the first 2 weeks post-MI while TIMP-1 and TIMP-2 protein levels were not significantly elevated until 2 weeks post-MI [26].
• In addition, secretion of plasminogen activators into the medium was unchanged after irradiation, while secretion of Timp2 increased [27].

Analytical, diagnostic and therapeutic context of Timp2

• CONCLUSIONS: Knock-down of TIMP-2 expression attenuates CCl(4)-induced liver fibrosis and is a potential pharmacological target for gene therapy in liver fibrosis [1].
• The levels of MMP-2, TIMP-2 and collagen IV (IV-C) protein in the kidney tissue were assessed by immunohistochemistry [2].
• Western blotting was used to identify a specific MMP, MMP2 (a gelatinase that digests basement membrane collagen and the dominant MMP observed on zymography) and a specific TIMP, TIMP2 [19].
• The contents of MMP-2 and TIMP-2 in culture supernatant were detected with ELISA and the activity of MMP-2 in supernatant was revealed by zymography [28].
• TIMP-2 mRNA was abundant in both subpopulations grown alone and did not change substantially upon coculture [29].

References