Disease relevance of TIMP2

• These results show that topical application of mitogenic bovine whey extract was able to modulate the expression of MMP-2, -9, and TIMP-2 in chronic leg ulcers and that its constituent growth factors may have the potential to redress the proteolytic imbalance observed in nonhealing chronic ulcers [1].
• We suggest the existence of a pertussis toxin sensitive G protein mediated mechanism for inhibition of Na+ dependent Ca2+ uptake in microsomes of bovine pulmonary artery smooth muscle under O2 *- triggered condition, which is regulated by PKCdelta dependent phosphorylation and sensitive to TIMP-2 for its inhibition [2].
• To determine the source of TIMPs in synovial fluids of patients with osteoarthritis (OA), the ability of chondrocytes to express TIMP-2 and its regulation by agents found in inflammed joints was investigated [3].
• Insulin stimulates secretion of a collagenase inhibitor by Swarm rat chondrosarcoma chondrocytes [4].
• Osteoclastic bone resorption was studied using 45Ca-labeled fetal rat bones cultured in the presence of parathyroid hormone (PTH) and an anti-invasion factor (AIF) derived from bovine hyaline cartilage which is enriched in a collagenase inhibitor [5].

Psychiatry related information on TIMP2

• 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 [6].

High impact information on TIMP2

• We have solved the 2.75 A crystal structure of the complex between the catalytic domain of human MT1-MMP (cdMT1-MMP) and bovine TIMP-2 [7].
• The collagen bundles were more often observed in the 12-day gland cultured in the presence of bovine dental pulp collagenase inhibitor, which had been shown to enhance cleft formation [8].
• 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 [9].
• The bovine cartilage-derived inhibitor exhibits greater than 65% homology over the first 23 residues with a collagenase inhibitor purified from human skin fibroblasts maintained in cell culture [10].
• Purification and partial amino acid sequence of a bovine cartilage-derived collagenase inhibitor [10].

Biological context of TIMP2

• Concentrations of TIMP-2 mRNA (picograms per microgram tissue DNA) were greater in corpora lutea collected during the early luteal phase (days 3 and 7) than the late luteal phase (day 16; P < 0.05) [11].
• TIMP-2 mRNA was also localized in a heterogeneous distribution within corpora lutea collected on days 3 and 10 post estrus (n = 3 each) [11].
• Giant binucleate cells expressed TIMP-2 during the whole gestation [12].
• In summary, MMP (gelatinases) and MMP inhibitors are present in developing luteal tissue, and the M(r) = 98 kDa enzyme, CDI, and TIMP-2 varied during the estrous cycle [13].
• The 25 kDa fragment enhanced the upregulation of MMP-2 and -9 and reduced TIMP-2 expression leading to CVEC chemoinvasion [14].

Anatomical context of TIMP2

• The treatment of BESCs with 12-O-tetradecanoylphorbol 13-acetate resulted in a significant increase in the level of TIMP-1 but a significant decrease in the level of TIMP-2 in the stromal cells [15].
• These results suggest that the expression of MMPs and TIMPs is differentially regulated by cytokines and growth factors and that the production of TIMP-1 and TIMP-2 may not be accompanied by changes in their mRNA expression in bovine endometrium and trophoblasts [15].
• Immunohistochemical analysis of ulcer biopsies for MMP-2, -9, and TIMP-2 expression showed a reduction in the number of MMP-2-positive dermal fibroblasts in the mitogenic bovine whey extract-treated ulcers compared with pretreatment biopsies (p<0.05) that persisted over the course of the study [1].
• The localization of proteins for MMP-1, MMP-14, and TIMP-2 showed a similar trend with strong staining intensity in cytoplasm of mammary duct and alveolar epithelial cells during pubertal mammogenesis and late involution [16].
• Pretreatment with vitamin E (1 mM) and TIMP-2 (50 microg/ml) reversed the effect produced by H2O2 (1 mM) on Na+ dependent Ca2+ uptake in the microsomes [17].

Associations of TIMP2 with chemical compounds

• The induction of TIMP-2 by ACTH required transcription, was mimicked by 8-bromo cyclic 3'-5' adenosine monophosphate, but was not observed in response to angiotensin II, IGF-1, fibroblast growth factor-2, transforming growth factor-beta1, or cortisol treatments [18].
• Matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitor-2 of matrix metalloproteinases (TIMP-2) in the placenta and interplacental uterine wall in normal cows and in cattle with retention of fetal membranes [12].
• Additionally, O2*- -induced inhibition of Na+-dependent Ca2+ uptake was reversed by SOD and TIMP-2 (50 microg ml(-1)) [19].
• The 72 kDa protease activity was found to be inhibited by EGTA and the tissue inhibitor of metalloprotease-2 (TIMP-2) [20].
• Heparin sepharose purified preparation of 72 kDa progelatinase is composed of two distinct population of zymogens: a 72 kDa progelatinase tightly complexed with TIMP-2 (an ambient tissue inhibitor of metalloprotease in the smooth muscle plasma membrane), and a native 72 kDa progelatinase free of any detectable TIMP-2 [21].

Physical interactions of TIMP2

• Heparin-sepharose (100 mM NaCl eluate)-purified preparation contained the MMP-2/TIMP-2 complex [22].

Regulatory relationships of TIMP2

• These results demonstrate that cellular outgrowth from bovine ICM is supported by fibronectin and is stimulated by TIMP-2 [23].

Other interactions of TIMP2

• In contrast, a transient increase in the number of MMP-9- and TIMP-2-positive cells was observed in mitogenic bovine whey extract treated ulcer biopsies compared with pretreatment levels (p<0.05) [1].
• The oxidant triggered protease activity and the Ca2+ATPase activity were found to be prevented by the antioxidant vitamin E, and also by the Ca2+ dependent matrix metalloprotease inhibitors: EGTA and TIMP-2 [20].
• Conversely, the 140 kDa fragment blocked MMP-2 and -9 stimulation and doubled TIMP-2 expression, leading to inhibition of endothelial chemoinvasion induced by fibroblast growth factor-2 (FGF-2) [14].
• Ovine large luteal cells may be the primary type of cell responsible for controlling the extent of remodelling of luteal ECM since they produce TIMP-1, TIMP-2 and plasminogen activator inhibitor 1 [24].
• RNAase dimer, PDC-109 and metalloproteinase inhibitor (TIMP-2) were identified [25].

Analytical, diagnostic and therapeutic context of TIMP2

• In situ hybridization localized TIMP-2 mRNA primarily to the thecal layer of post-surge follicles (n = 3) [11].
• Tissue inhibitor of metalloproteinase 2 (TIMP 2) was detected by ELISA in healthy tissue [26].
• The three-dimensional structure of human tissue inhibitor of metalloproteinases-2 (TIMP-2) was determined by X-ray crystallography to 2.1 A resolution [27].
• Mobility of the 24 kDa heparin-binding protein increased under nonreducing SDS-PAGE to approximately 21 kDa, characteristic of the reported molecular mass of TIMP-2 [28].
• Expression of TIMP-2 mRNA was detected by RT-PCR in bovine bulbourethral gland, prostate, and seminal vesicles [28].

References