Disease relevance of MMP10

• The catalytic domain of matrix metalloproteinase-10 (MMP-10) has been expressed in Escherichia coli and its crystal structure solved at 2.1 A resolution [1].
• MMP-10 was expressed widely in the epithelium of all SCC specimens. alphavbeta6 integrin expression was also detected in some cases of epithelial hyperplasia but was significantly more abundant in cancers at the invasive front [2].
• In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)--were used to examine the expression of these three different MMPs in human gastric and colonic carcinomas and in adjacent normal mucosa [3].
• Overexpression of MMP 10 and MMP 11 correlated with higher grade for NSCLC (p = 0.029 and p = 0.016, respectively), and also in a subset of adenocarcinomas (AC) (p = 0.015 and p = 0.009, respectively) [4].
• Our approach revealed that MMP-10 plays an important role in the recurrence in stage IB lung cancer, irrespective of the histologic type [5].

Psychiatry related information on MMP10

• We observed downregulation of several matrix metalloproteinases (MMPs), i.e., MMPI and MMP3, and MMP10 in the transfected cells [6].
• The resting pain threshold decreased and exercise-induced muscle soreness subsequently increased at BC (p < 0.05 vs. SL1/SL2) [7].

High impact information on MMP10

• Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10 [8].
• SL-1 constitutes a novel member of the RSRF family whilst SL-2 is similar to human RSRFC4 throughout its length [9].
• A binding activity, antigenically related to both human RSRFC4 and the SL-2 gene product, is detected in Xenopus embryos and after gastrulation is localized to embryonic muscle [9].
• Because remodeling of airway epithelium is a feature of chronic asthma, the up-regulation of MMP10 and TIMP3 by NPS-NPSR1 signaling may be of relevance in the pathogenesis of asthma [10].
• Using MMP inhibitors and MMP-specific small interfering RNA, we show that MMP function confers protection from PKC/p53-induced apoptosis and identify the protective MMPs as MMP-9 and MMP-10 [11].

Biological context of MMP10

• Crystal structure of the catalytic domain of human matrix metalloproteinase 10 [1].
• The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro [12].
• Microarray analysis and RNase protection assays showed that ZNF267 represses MMP-10 gene expression, which was confirmed by reporter gene assays [13].
• Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays [13].
• In the dimer, two self-complementary sequences, PAL1 and PAL2, form intermolecular duplexes, and an SL1-SL2 (stem-loop) domain forms loop-loop base pairs, mediated by GACG tetraloops, and extensive tertiary interactions [14].

Anatomical context of MMP10

• MMP-10 overexpressed in the diabetic corneal epithelium seems to be the major contributor to the observed changes in DR corneas [15].
• Overexpression of matrix metalloproteinase-10 and matrix metalloproteinase-3 in human diabetic corneas: a possible mechanism of basement membrane and integrin alterations [15].
• Within the rib, active SL-2 expression was localized in chondrocytes of the growth plate, whereas only occasional SL-1 signal was evident [12].
• SL-2, but not SL-1, was strongly expressed in osteoclasts and most mononuclear cells within the marrow [12].
• Among stromelysins, MMP-3 mRNA could not be detected in any cell line, while MMP-10 mRNA was expressed in all of them, although at variable levels [16].

Associations of MMP10 with chemical compounds

• In summary, our work demonstrates that MMP-1 zymogen activation is mediated by multiple serine proteases and MMP-10, and that these events are central to EC-mediated collagen degradation and capillary tube regression in 3D collagen matrices [17].
• Beta-carotene dose-dependently quenched (1)O(2)-mediated induction of MMP-1 and MMP-10 [18].
• Multiple alignment analysis of the amino acid sequence revealed that HcSP-1 is most similar to SL-1 from S. litura (73.8% identity) and other methionine-rich hexamers, whereas HcSP-2 is most similar to the SL-2 alpha subunit from S. litura (74.8% identity) and other moderately methionine-rich hexamers [19].
• The spin labeled acetylcholine analog, SL-2, which is a potent, non-stimulating muscarinic antagonist on the isolated frog heart, is a potent agonist a low concentrations (3x10-5 M) and an antagonist at slightly higher concentrations (4.5x10-5 M) on the mixed cholinergic receptors of the leech [20].
• The serum concentration of lipid hydroperoxides (LH) increased markedly at rest and after maximal exercise at BC (p < 0.05 vs. SL1/SL2) whereas no changes were observed for plasma malondialdehyde (MDA) [7].

Regulatory relationships of MMP10

• ECs expressing increased levels of MMP-10 activated MMP-1 to a greater degree than control ECs [17].
• We also found that 6/8 MM cell lines expressed MMP-7 (matrilysin) and 3/8 MM cell lines expressed MMP-10 (stromelysin-2) [21].
• The latent SL-2 proenzyme was isolated from 12-O-tetradecanoylphorbol-13-acetate-induced keratinocytes by immunoaffinity chromatography using a cross-reactive antibody raised against human SL-1 [22].

Other interactions of MMP10

• Comparative studies using zymography and PCR analysis demonstrated differences in MMP-2 and MMP-10 expression between the 3 cultures [23].
• Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10 [24].
• CXCL12 also significantly increased stromelysin-2 (MMP-10) expression by LNCaP cells [25].
• In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis through alteration of matrix degradation in vivo [13].
• Also, MMP 10 and MMP 11 correlated with lymph node involvement in NSCLC (p = 0.025 and p = 0.027 respectively) [4].

Analytical, diagnostic and therapeutic context of MMP10

• We investigated the presence of SL-1 and SL-2 in human osteophytic and neonatal rib bone using immunohistochemistry and, combined with a new method of in situ zymography, determined the activity of the immunolocalized stromelysins [12].
• Immunolocalization of CRP, MMP-1, and MMP-10 was performed in human mammary arteries and carotid endarterectomy specimens [26].
• Synovial fluid levels of MMP-10 were determined by specific immunoassay [27].
• On transcriptional assay by quantitative RT-PCR and real-time RT-PCR analysis to validate those molecules, both transcripts of MMP-10 and MMP-12 were significantly more upregulated in recurred stage IB lung cancer than in the non-recurred stage IB lung cancer (P=0.004) [5].
• Organ cultures were treated with a cathepsin inhibitor, cystatin C, or MMP-10 [28].

References