Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical observations suggest that patients with coronary artery disease (CAD) display a marked heterogenerty in collateral formation despite similar degrees of coronary obstruction. The development of coronary collaterals helps protect the myocardium from ischemic damage, yet the factors responsible for collateral formation are poorly understood. To better understand the biochemical and cellular mechanisms of collateral artery formation, monocyte function and circulating levels of pro- and antiangiogenic factors were measured in 101 patients with angiographically assessed CAD and extensively developed (score 2, n = 33) or absent (score 0, n = 68) collateral circulations. Compared with patients with score 0, those with score 2 were slightly older and had more advanced CAD. The score 2 group was also more likely to have had a previous myocardial infarction or coronary artery bypass grafting and a family history of CAD. At the same time, there were no significant differences between groups with regard to circulating levels of vascular endothelial growth factor-A(165), platelet-derived growth factor-betabeta, fibroblast growth factor-2, fibroblast growth factor-4, hepatocyte growth factor, tumor necrosis factor-alpha, interleukin-1beta, endostatin, matrix metalloproteinase-9, promatrix metalloproteinase-1, and CD40 ligand. Monocytes isolated from patients with score 2 and 0 collateral circulations demonstrated no differences in migration assays. However, adhesion to fibrinogen and collagen was significantly higher for monocytes from patients with score 0 (p = 0.05 and 0.04, respectively). In conclusion, these data suggest that the degree of coronary collateral formation is not determined by differences in systemically measurable levels of pro- or antiangiogenic factors assessed in this study. Rather, cellular properties, such as cell adhesion, or genetic differences between patients may be the driving force for collateral development.
 ...
PMID:Humoral and cellular factors responsible for coronary collateral formation. 1705 26

Hypoxia is associated with extracellular matrix remodeling in several inflammatory lung diseases, such as fibrosis, chronic obstructive pulmonary disease, and asthma. In a human cell culture model, we assessed whether extracellular matrix modification by hypoxia and platelet-derived growth factor (PDGF) involves the action of matrix metalloproteinases (MMPs) and thereby affects cell proliferation. Expression of MMP and its activity were assessed by zymography and enzyme-linked immunosorbent assay in human lung fibroblasts and pulmonary vascular smooth muscle cells (VSMCs), and synthesis of soluble collagen type I was assessed by enzyme-linked immunosorbent assay. In both cell types, hypoxia up-regulated the expression of MMP-1, -2, and -9 precursors without subsequent activation. MMP-13 was increased by hypoxia only in fibroblasts. PDGF-BB inhibited the synthesis and secretion of all hypoxia-dependent MMP via Erk1/2 mitogen-activated protein (MAP) kinase activation. Hypoxia and PDGF-BB induced synthesis of soluble collagen type I via Erk1/2 and p38 MAP kinase. Hypoxia-induced cell proliferation was blocked by antibodies to PDGF-BB or by inhibition of Erk1/2 but not by the inhibition of MMP or p38 MAP kinase in fibroblasts. In VSMCs, hypoxia-induced proliferation involved Erk1/2 and p38 MAP kinases and was further increased by fibroblast-conditioned medium or soluble collagen type I via Erk1/2. In conclusion, hypoxia controls tissue remodeling and proliferation in a cell type-specific manner. Furthermore, fibroblasts may affect proliferation of VSMC indirectly by inducing the synthesis of soluble collagen type I.
 ...
PMID:Cell type-specific effect of hypoxia and platelet-derived growth factor-BB on extracellular matrix turnover and its consequences for lung remodeling. 1709 19

The creation of tissue-engineered constructs with autologous cells is a central goal in regenerative medicine. With respect to ligament replacement, we have evaluated the influences of matrix and growth factors on hMSCs (human mesenchymal stromal cells). hMSCs were seeded in two different 3D (three-dimensional) systems consisting of either a collagen type I gel or a synthetic PLA [poly-(L-lactic acid)] scaffold. After cultivation for 14 days with rhTGFbeta1 (recombinant human transforming growth factor beta1), rhPDGF-BB (recombinant human platelet-derived growth factor homodimer of B-chain) or rhBMP13 (recombinant human bone morphogenetic protein 13), we assessed the proliferation potential, mRNA expression and protein expression of various matrix-interacting and matrix-degrading molecules by quantitative real-time RT (reverse transcriptase)-PCR, immunohistochemistry and gelatin zymography in comparison with unstimulated cells. Cellular reactions to the type of scaffold or soluble factors could be found in the expression of tenascin-C as well as integrin subunits alpha1, alpha3 and beta1. Collagen type X expression was induced by 3D culture and stimulated by rhTGFbeta1 on PLA. The expression of MMP-1 (matrix metalloproteinase 1) tended to increase, and MMP-13 was induced in the collagen culture system. The activation of MMP-2 was stimulated by the cultivation of MSCs within the collagenous matrix. These results demonstrated that various interactive effects of growth factors and scaffolds influence the cell-biological behaviour of MSCs. It is important to take these complex interactions, which partly differ from differentiated cells, into account in further tissue-engineering approaches.
 ...
PMID:Interactive effects of growth factors and three-dimensional scaffolds on multipotent mesenchymal stromal cells. 1764 Jan 72

Wound fluids, human serum from platelet-poor and platelet-rich plasma (SPPP and SPRP), contain various soluble factors involved in cell growth and proliferation. Levels of cytokines, chemokines, and matrix metalloproteinases (MMPs) in drainage fluids (DFs) harvested from subcutaneous wounds, punctured fluids (PF) from seroma, and SPPP were measured. SPPP and SPRP from four healthy volunteers were also subjected to the analysis. Biochemical profiles of DF reflected the sequential stages of wound healing. Early-phase DF contained high concentrations of basic fibroblast growth factor and platelet-derived growth factor and EGF. The levels of keratinocyte growth factor, interleukin-6, and MMP-8 in DF peaked on days 2-3, while vascular endothelial growth factor, hepatocyte growth factor, interleukin-8, and MMP-1 increased over time during days 0-6. Punctured fluids contained high levels of TGF-beta1, keratinocyte growth factor, vascular endothelial growth factor, hepatocyte growth factor, and MMP-1. Experiments using human adipose-derived stem cells and dermal fibroblasts cultured in media containing various concentrations of DF and fetal bovine serum suggested that for some cell types, DF-contained growth factors that are not obtained from SPRP could be used to supplement or substitute for serum in culture media. SPRP and DF are economical ready-made mixtures of serum and autologous soluble factors, and may be differentially useful for regenerative therapies.
 ...
PMID:Characterization of wound drainage fluids as a source of soluble factors associated with wound healing: comparison with platelet-rich plasma and potential use in cell culture. 1765 95

Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis. In response to liver injury, HSCs undergo a process called activation, which involves 2 steps jonit nation from quiescent phenotype to myofibroblast-like phenotype, and perpetuation that maintains the activated phenotype of HSCs. The fate of the activated HSCs depends on the apoptotic and survival signals that they receive. The apoptosis of HSCs results from a series of complex and interrelated signaling events. Apoptotic signals for the activated HSCs include proteins from membrane receptors, such as death receptors, nerve growth factor receptor and peripheral-type benzodiazepine receptor, as well as proteins from cytoplasm such as Bcl-2 family members. The survival signals for the activated HSCs are induced by some kinases and cytokines including tissue inhibitors of metalloproteinase-1, Rho/Rho kinase, platelet-derived growth factor, transforming growth factor beta-1, and insulin-like growth factor-1. Approaches that specifically initiate HSC apoptosis are promising to be direct and effective strategies to treat liver fibrosis. Although it remains unclear whether the activated HSCs could be reversed back to the quiescent phenotype, the different expression and sensitivity of pro-apoptotic and survival molecules between quiescent and activated HSCs provide a prospect to develop therapeutic approaches that specifically targets apoptosis of the activated HSCs. These therapeutic strategies to induce HSC apoptosis are current research hotspot and the future for the patients with liver fibrosis and cirrhosis.
 ...
PMID:Apoptotic and survival signals in hepatic stellate cells. 1800 61

The genes that mediate fibroproliferative lung disease remain to be defined. Prior studies from our laboratory showed by in situ hybridization and immunohistochemistry that the genes coding for tumour necrosis factor alpha, transforming growth factor beta, the platelet-derived growth factor A and B isoforms, and alpha-1 pro-collagen are expressed in fibroproliferative lesions that develop quickly after asbestos inhalation. These five genes, along with matrix metalloproteinase 9, a collagenase found to be increased in several lung diseases, are known to control matrix production and cell proliferation in humans and animals. Here we show by laser capture microdissection that (i) The six genes are expressed at significantly higher levels in the asbestos-exposed mice when comparing the same anatomic regions 'captured' in unexposed mice. (ii) The bronchiolar-alveolar duct (BAD) junctions, where the greatest number of fibres initially deposit, were always significantly higher than the other anatomic regions for each gene. The first alveolar duct bifurcation (ADB) generally was higher than the second ADB, the ADBs were always significantly higher than the airway walls and pleura, and the airway walls and pleura were generally higher than the unexposed tissues. (iii) Animals exposed for 3 days always exhibited significantly higher levels of gene expression at the BAD junctions and ADBs than animals exposed for 2 days. To our knowledge, this is the first demonstration of a dose-response to a toxic particle in situ, and this response appears to be dependent on the number of fibres that deposits at the individual anatomic site.
 ...
PMID:Laser capture microdissection reveals dose-response of gene expression in situ consequent to asbestos exposure. 1803 78

In search of an autologous vascularized skin substitute, we treated full-thickness wounds (FTWs) with autologous platelet-rich plasma gel (APG) in which we embedded endothelial progenitor cells (EPCs) and basal cell keratinocytes (KCs). We cultivated autologous KCs in low-serum conditions and expanded autologous EPCs from venous blood. FTWs (n = 55) were created on the backs of four pigs, covered with wound chambers, and randomly assigned to the following treatments: (1) APG, (2) APG + KCs, (3) APG + EPCs, (4) APG + KCs + EPCs, and (5) saline. All wounds were biopsied to measure neovascularization (lectin Bandeiraea Simplicifolia-1 (BS-1), alpha smooth muscle actin [alphaSMA], and membrane type 1 matrix metalloproteinase (MT1-MMP)), matrix deposition (fibronectin, collagen type I/III, and alphavbeta3), and reepithelialization. Wound fluids were analyzed for protein expression. All APG-treated wounds showed more vascular structures (p < 0.001), and the addition of EPCs further improved neovascularization, as confirmed by higher lectin, alphaSMA, and MT1-MMP. APG groups had higher collagen I/III (p < 0.05), alphavbeta3, and fibronectin content (p < 0.001), and they exhibited higher concentrations of platelet-derived growth factor subunit bb, basic fibroblast growth factor, hepatocyte growth factor, insulin growth factor-1, transforming growth factor-beta1 and -beta3, matrix metalloproteinase-1 and -z9, and tissue-inhibiting matrix metalloproteinase-1 and -2. Applying APG + KCs resulted in the highest reepithelialization rates (p < 0.001). No differences were found for wound contraction by planimetry. In this porcine FTW model, APG acts as a supportive biomatrix that, along with the embedded cells, improves extracellular matrix organization, promotes angiogenesis, and accelerates reepithelialization.
 ...
PMID:A plasma-based biomatrix mixed with endothelial progenitor cells and keratinocytes promotes matrix formation, angiogenesis, and reepithelialization in full-thickness wounds. 1908 5

Platelet derived growth factor (PDGF) is involved in wound healing in various organ systems. Its potential role in the context of peritoneal injury following long-term peritoneal dialysis is unclear. We used an adenovirus expressing the B chain of PDGF (AdPDGF-B) to assess its effect on pro-fibrotic pathways in the peritoneal membrane. To assess the transforming growth factor (TGF) beta independent effects of PDGF, we over-expressed PDGF-B in the peritoneum of either wild-type mice (Smad3+/+) or those with a deletion of the TGFbeta signaling protein Smad3 (Smad3(-/-)). PDGF-B induced sustained angiogenesis in both Smad3+/+ and Smad3(-/-) mice. Despite increased collagen gene expression, collagen accumulation was transient and fibrogenesis was associated with induction of collagenase activity. We observed epithelial to mesenchymal transition (EMT) involving the peritoneal mesothelial cells, as shown by increased SNAIL and decreased E-Cadherin expression with evidence of mesothelial cells expressing both epithelial and mesenchymal markers. Unlike TGFbeta-induced EMT, PDGF-B exposure did not lead to mobilization of the mesothelial cells; they remained as a single monolayer throughout the observation period. This "non-invasive" EMT phenomenon is a novel finding and may have implications concerning the role of EMT in peritoneal fibrosis and injury to other organ systems. The observed effects were similar in Smad3(-/-) and Smad3+/+ animals, suggesting that the PDGF-B effects were independent of TGFbeta or Smad signaling.
 ...
PMID:Platelet derived growth factor B and epithelial mesenchymal transition of peritoneal mesothelial cells. 1989 31

Vascular endothelial growth factor (VEGF), which is a key regulator of angiogenesis, often induces formation of immature vessels with increased permeability and reduced vessel functionality. Here, we demonstrate that de novo expression of murine (m)VEGF-164 induces malignant and invasive tumor growth of HaCaT keratinocytes. However, the mVEGF-164-induced tumors are ulcerated with a disorganized epithelium that is interrupted by lacunae with limited basement membrane and endothelial cell coverage. Vessel maturation is strongly impaired. Tumor and vessel micromorphology are markedly improved by the combined expression of human platelet-derived growth factor (hPDGF)-B and mVEGF-164. Although tumor size and malignancy are comparable with either mVEGF-164 alone or combined human PDGF-B and mVEGF-164 expression, combined hPDGF-B and mVEGF-164 expression leads to a more solid and compact tumor tissue with a mature functional tumor vasculature and a higher microvessel density, as demonstrated histologically and by dynamic contrast-enhanced magnetic resonance imaging. Treatment of the hPDGF-B- and mVEGF-164-expressing tumors with imatinib mesylate to block PDGF-B signaling reverses this effect. In addition, tumor cell invasion of mVEGF-164 transfectants and mVEGF-164 plus hPDGF-B transfectants in vivo is associated with a marked induction of tumor-derived matrix metalloproteinase-1 and stromal matrix metalloproteinase-9 and -13, as was confirmed in three-dimensional organotypic co-cultures with fibroblasts in vitro. These data clearly demonstrate the need for a concerted action of different growth factors in the establishment of solid tumors with functional vasculature and emphasize the need for a multifactorial therapy.
 ...
PMID:Platelet-derived growth factor-B normalizes micromorphology and vessel function in vascular endothelial growth factor-A-induced squamous cell carcinomas. 2004 79

Objective. To examine new investigative biomarkers and their relevance for radiographic severity in knee osteoarthritis. Methods. The group comprised 63 patients with 73 knees examined. Patients were divided according to radiographic severity to allow for comparison of biomarker levels. Hyaluronic acid (HA), matrix metalloproteases (MMP-1, MMP-3 and MMP-13), tissue inhibitors of metalloproteases (TIMP-1 and TIMP-2), platelet-derived growth factor (PDGF-AB), transformed growth factor (TGF-beta), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and insulin-like growth factor (IGF-I) were measured on synovial fluid and in plasma releasate at a single time point. Principal component analysis (PCA) followed by analysis of covariance were applied to evaluate data. Results. Four different groups of biomarker were identified in plasma releasates. The first (platelet number, PDGF-AB and TGF-beta) and second groups (HA and IGF-I) were related to radiographic severity, P = .005 and P = .022, respectively. The third (MMP-1 and TIMP-2) and fourth groups (MMP-3 and TIMP-1) represented the catabolic balance, but were not associated to radiographic grading. Three different clusters of biomarkers were found in synovial fluid but did not show any significant association to radiographic grading. Conclusions. New imaging approaches to assess structural deterioration and correlation with biomarker levels are warranted to advance in OA research.
 ...
PMID:Relationship between Investigative Biomarkers and Radiographic Grading in Patients with Knee Osteoarthritis. 2013 Aug 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>