Disease relevance of Timp3

• TIMP-3 Ameliorates Hepatic Ischemia/Reperfusion Injury Through Inhibition of Tumor Necrosis Factor-Alpha-Converting Enzyme Activity in Rats [1].
• In contradistinction to TIMP-1, a decrease in TIMP-3 mRNA levels was noted at 12 h after ureteral obstruction and persisted at the 24-, 48-, and 96-h time intervals [2].
• ADAM-17 and TIMP3 protein and mRNA expression in spinal cord white matter of rats with acute experimental autoimmune encephalomyelitis [3].
• MMP-2, MMP-9 and TIMP-3 seem to play a critical role in the development of fibrosis in the renal allograft [4].
• The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contributing to brain injury [5].

Psychiatry related information on Timp3

• Furthermore, the shedding process appears to be regulated under physiologic conditions, because a putative inhibitor of the shedding process, tissue inhibitor of metalloprotease-3 (TIMP-3), is increased by food deprivation [6].

High impact information on Timp3

• Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis [7].
• However, little is known about the mechanisms underlying TIMP-3-induced apoptosis [8].
• The A and B beta-strands of the N-terminal domain of TIMP-3 contain two potential heparin-binding sequences rich in lysine and arginine; these strands should form a double track on the outer surface of TIMP-3 [9].
• The present results show that glycosaminoglycans such as heparin, heparan sulfate, chondroitin sulfates A, B, and C, and sulfated compounds such as suramin and pentosan efficiently extract TIMP-3 from the postpartum rat uterus [9].
• Confocal microscopy shows colocalization of heparan sulfate and TIMP-3 in the endometrium subjacent to the lumen of the uterus [9].

Biological context of Timp3

• With continued luteal development, there was a homogenous, intense localization of TIMP-3 mRNA throughout the CL, which was unchanged during pseudopregnancy [10].
• TIMP2 was also significantly up-regulated in the DREZ and degenerating dorsal column, where TIMP1 and TIMP3 showed only moderate up-regulation [11].
• Expression of TIMP-3 mRNA decreased significantly between proestrus and estrus [12].
• TIMP-1 and TIMP-3 mRNAs, which were low to undetectable in the granulosa cells of preovulatory follicles, were greatly increased in the luteinizing cells of newly forming CL on estrus [12].
• Sequence analysis reveals an open reading frame containing 211 amino acids that show 99% identity to mouse TIMP-3 and 95% identity to human TIMP-3, respectively [13].

Anatomical context of Timp3

• TIMP-1 coding m-RNAs were present mainly in hepatic stellate cells and rat liver myofibroblasts, TIMP-2 additionally in Kupffer cells, while TIMP-3 expression was detectable only in hepatocytes [14].
• TIMP-3 mRNA was present in the granulosa cells of certain follicles but was absent in granulosa cells of adjacent follicles [15].
• At Day 1 of pseudopregnancy, intense reaction product for TIMP-3 mRNA was observed in granulosa-lutein cells of certain developing CL, whereas adjacent follicles did not express TIMP-3 mRNA [10].
• TIMP-2 and TIMP-3 immunoreactivities were induced in activated astrocytes in deep cortex and the underlying white matter [16].
• In conclusion, our studies indicate that BMP-2 suppresses collagenase-3 gene transcription and stimulates TIMP 1 and TIMP 3 expression in osteoblasts [17].

Associations of Timp3 with chemical compounds

• Alendronate did not alter the expression of TIMP 1 and 2, but modestly stimulated the expression of TIMP 3 [18].
• It also inhibited genes involved in estradiol (P-450(AROM)) and cholesterol biosynthesis (HMG-CoA synthase), as well as genes involved in tissue remodeling: VEGF and TIMP3 [19].
• LH alone or with genistein did not alter the expression of mRNA encoding TIMP-2 and TIMP-3, or mRNA encoding gelatinases A and B. These data indicate that tyrosine kinases play a role in the LH-induced tissue remodelling required for ovulation by mediating the LH-stimulated expression of collagenase 3 [20].
• In this study we show that overexpression of TIMP-3 by adenovirus-mediated gene transfer partially protects neurons against excitotoxic death induced by glutamate in culture [21].

Other interactions of Timp3

• TIMP-2 and TIMP-3 transcripts become detectable on day 10 and remained stable afterwards [22].
• Amelioration of hepatic ischemia/reperfusion injury after inhibition of TACE activity by TIMP-3 suggests that TACE inhibition may play an important role in preventing liver ischemia/reperfusion injury warranting further experimental and clinical study [1].
• In contrast, TIMP-1 and TIMP-3 expression in E19 scarring wounds increased six-fold and four-fold, respectively [23].
• Both MMP-9 and TIMP-3 were regulated by various cytokines [16].
• Taken together, our results suggest that MMP-2 and TIMP-3 may have functional roles in rat luteal formation, while TIMP-2 may be implicated in both formation and regression of the pregnant CL [24].

Analytical, diagnostic and therapeutic context of Timp3

• We have cloned the cDNA encoding the rat tissue inhibitor of metalloproteinase 3 (TIMP-3) by a PCR cloning method [13].
• TIMP-3 mRNA expression was downregulated in allografts [4].
• Gelatinolytic activity of MMP-2 and -9 were demonstrated by zymography, and MMP-2,-9 and TIMP-3 mRNA by in situ hybridization [4].
• Western blots were used to measure TIMP-3 protein expression [25].
• Dual-fluorescence staining for TUNEL and TIMP-3 showed that they were coexpressed in many neurons [25].

References