Disease relevance of Ecm1

• HHcy is associated with activation of matrix metalloproteinases (MMPs); however, it is unclear whether HHcy-dependent extracellular matrix (ECM) accumulation plays a role in arterial hypertrophy and hypertension [1].
• HHcy caused increased aortic blood pressure and resistance, tachycardia, and increased wall thickness and ECM accumulation in aortic wall vs. control groups [1].
• The production of extracellular matrix proteins is an important element of tumor formation, and alterations in matrix protein metabolism may be critical to the process of tumor metastasis [2].
• Microarray studies showed no incresae in these ECM factors, rather down-regulation of urokinase-type plasminogen activator and matrix metalloproteinase 16 in glioblastoma cells treated with OA-5D5 [3].
• Fibrosis is a consequence of injury characterized by accumulation of excess collagen and other extracellular matrix components, resulting in the destruction of normal tissue architecture and loss of function [4].

Psychiatry related information on Ecm1

• They have a postulated role in remodeling of extracellular matrix and defense mechanisms against chitin-containing pathogens [5].

High impact information on Ecm1

• We show that histone deacetylase 7 (HDAC7) is specifically expressed in the vascular endothelium during early embryogenesis, where it maintains vascular integrity by repressing the expression of matrix metalloproteinase (MMP) 10, a secreted endoproteinase that degrades the extracellular matrix [6].
• Elastic fibers are components of the extracellular matrix and confer resilience [7].
• MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components [8].
• Layering of neurons in the cerebral cortex and cerebellum requires Reelin, an extracellular matrix protein, and mammalian Disabled (mDab1), a cytosolic protein that activates tyrosine kinases [9].
• Basement membranes are composed of ordered arrays of characteristic extracellular matrix proteins, but little is known about the assembly of these structures in vivo [10].

Chemical compound and disease context of Ecm1

• Extracts of the EHS tumor, which produces an extracellular matrix containing basement membrane components, were tested for their ability to promote attachment to cycloheximide-treated PAM 212 cells [11].
• Collectively, our data suggests that interactions between a cell surface CD44-related CSPG and type I collagen in the ECM may play an important role in mouse melanoma cell motility and invasion, and that the chondroitin sulfate portion of the proteoglycan seems to be a critical component in mediating this effect [12].
• Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase [13].
• Osteopontin (OPN) is an extracellular matrix protein containing Arg-Gly-Asp (RGD) sequence, which interacts with alpha(v)beta3 integrins, promotes cell attachment, and cell migration and is expressed in both synovial cells and chondrocytes in rheumatoid arthritis; however, its functional relationship to arthritis has not been known [14].
• We now report that among the breakdown products of the ECM generated by heparanase is a trisulfated disaccharide that can inhibit delayed-type hypersensitivity (DTH) in mice [15].

Biological context of Ecm1

• We studied Ecm1 mRNA expression and localization during endochondral bone formation and investigated the effect of recombinant human (rh) Ecm1a protein on organ cultures of embryonic mouse metatarsals [16].
• We have analysed the Ecm1 regulatory elements by reporter gene constructs and transient transfections in the stromal osteogenic cell line MN7 [17].
• Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice [18].
• Extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases [MMPs] contributes to progressive left ventricular remodeling, dilation, and heart failure [18].
• The extended open reading frame of the 8.5-kb mRNAs code for domains already identified in the 6.6-kb mRNA, including two different types of calcium-binding motifs and a region with a highly conserved cysteine pattern similar to that found in Ecm1 in the mouse [19].

Anatomical context of Ecm1

• In situ hybridization and immunohistochemistry demonstrated Ecm1 expression in the connective tissues surrounding the developing bones, but not in the cartilage [16].
• Ecm1 expression was not found in 16- and 17-day-old metatarsals of which the perichondrium was removed [16].
• We tested the hypothesis that in HHcy the mechanism of arterial hypertension involves arterial dysfunction in response to ECM accumulation between endothelial and arterial smooth muscle cells and subsequent endothelium-myocyte (E-M) uncoupling [1].
• IGFBP-5 mediates its profibrotic effects through fibroblast activation, increased ECM deposition, and myofibroblastic transformation of dermal fibroblasts [20].
• Notably, neutrophilic infiltrates were significantly reduced in MMP-9(-/-) mice, owing perhaps to limited release of Pro-Gly-Pro, a potent neutrophil chemotactic tripeptide released from extracellular matrix through the action of MMP-9 [21].

Associations of Ecm1 with chemical compounds

• BACKGROUND: Matrix metalloproteinases play a crucial role in the regulation of extracellular matrix turnover and structural artery wall remodeling [22].
• In addition to ERK activation, an inflammatory stimulus, such as low m.w. hyaluronic acid from the extracellular matrix, must also be present [23].
• Estrogen may be an important regulator of fibulin-3 expression, and this highlights a novel mechanism by which circulating estrogen may control the composition of the retinal extracellular matrix [24].
• Because hCG regulated proteases and SERPINs (whereas testosterone did not), it could alter the proteolytic balance of Leydig cells and consequently the metabolism of extracellular matrix components [25].
• JF-10-81 was found to block PC-3 cell attachment to various extracellular matrix components, mainly to vitronectin, the ligand of cell surface receptors integrin alphaVbeta3 and alphaVbeta5 [26].

Physical interactions of Ecm1

• Fibulin-2, an extracellular matrix protein containing tandem arrays of calcium-binding epidermal growth factor-like motifs, is present in the basement membrane and stroma of many tissues [27].
• We have also demonstrated that phosphorothioate homopolymers of cytidine and thymidine release bFGF bound to low affinity receptors in extracellular matrix (ECM) [28].
• Collagenase was found within some cells of the primary tumour and also bound to the extracellular matrix at discrete sites [29].
• Further analysis of v-rasHa-transformed EGFR-deficient keratinocytes in vitro indicated that such cells migrated more on and attached less to extracellular matrix components [30].
• The catalytic activity of c-Abl tyrosine kinase is reduced in fibroblasts that are detached from the extracellular matrix [31].

Enzymatic interactions of Ecm1

• We have demonstrated that the mesangial extracellular matrix is susceptible to metal-catalyzed oxidation and that this increases scavenger receptor-mediated adhesion of macrophages, cells which appear to be important participants in glomerular injury via their secretory products [32].
• Dentin matrix protein 1 (DMP1) is one of the acidic phosphorylated extracellular matrix proteins called the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family [33].
• Type IV collagenase plays an important role in tumor invasion and metastasis through cleaving type IV collagen in the basement membrane and extracellular matrix [34].

Regulatory relationships of Ecm1

• These results indicate that targeting Sp1 efficiently blocks extracellular matrix gene expression, and suggest that such an approach may represent an interesting therapeutic alternative toward the treatment of fibrotic disorders [4].
• We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis [35].
• PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model [35].
• Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions [36].
• Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production [37].

Other interactions of Ecm1

• Tumor cells are capable of degrading the extracellular matrix via a proteolytic cascade that includes urokinase-type plasminogen activator (uPA) and matrix metalloproteases (MMPs) [38].
• Up-regulation of mRNA for 2 extracellular matrix proteins was observed in the Tsk2 dermal fibroblasts compared with the normal cells: the alpha1(I) procollagen mRNA steady-state levels were 50% higher, and those of the alpha1(III) procollagen mRNA 100% higher, in Tsk2 cells [39].
• The retinoblastoma protein modulates expression of genes coding for diverse classes of proteins including components of the extracellular matrix [40].
• The Mfap2 gene encodes the microfibril-associated glycoprotein-1 (MAGP1), an extracellular matrix protein of microfibrillar structures [41].
• Transforming growth factor-beta1 (TGFbeta) is a strong activator of extracellular matrix accumulation [42].

Analytical, diagnostic and therapeutic context of Ecm1

• Molecular cloning and characterization of the mouse Ecm1 gene and its 5' regulatory sequences [17].
• Simultaneously reduced expression of several extracellular matrix genes as compared with mock-transfected clones was noted using differential hybridization of cDNA microarrays, without significant alteration in cell growth [4].
• Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting [43].
• These mice may serve as an animal model to study the role of ECM proteins in osteoporosis [44].
• To move forward, migrating cells must generate traction forces through surface receptors bound to extracellular matrix molecules coupled to a rigid structure [45].

References