Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this investigation was to examine the role that keratinocyte growth factor (KGF) plays in the control of matrix-degrading protease activity in epithelial cells. The culture conditions had a significant effect on cellular responses to the growth factor. In histiotypic culture on porous-polycarbonate membranes, porcine periodontal ligament epithelial cells responded to KGF with increased 92-kDa gelatinase (matrix metalloproteinase [MMP]-9) activity. No such response was observed in cells maintained on plastic plates. Epidermal growth factor and platelet-derived growth factor also increased MMP-9 activity in the histiotypic cultures of epithelial cells. Addition of heparin with KGF produced a further increase in MMP-9 activity, with heparin alone having no effect. Precoating of polycarbonate membranes with matrix components showed that fibronectin and an engineered poly-RGD molecule substrate were required for KGF plus heparin to increase MMP-9 activity. Precoating plastic culture plates with the same proteins did not generate the same response. Concomitant with gelatinase activity, KGF also increased urokinase-type plasminogen activator in the epithelial cells. Thus, KGF appears to be an important regulator of protease secretion in epithelial cells.
 ...
PMID:Keratinocyte growth factor stimulation of gelatinase (matrix metalloproteinase-9) and plasminogen activator in histiotypic epithelial cell culture. 776 70

Migration to the intima and other responses of M-SMC in the rat carotid artery and abdominal aorta after balloon injury were investigated in vivo. Migration occurred intensively between the second and fifth days after injury. About 80% of the cells were in the G1 and S phases of the cell cycle. The majority of the migrating cells were therefore simultaneously proliferating. Positive values of 42.3%, 48.9%, 44.4%, and 32.8% of the migrating cells on the fifth day in the carotid artery for PDGF-B, elastase III B, MMP-I, and MMP-9, were observed, respectively. Many of the cells expressed messages of PDGF-A and elastases II and III B by in situ hybridization. Fine structures of the migrating cells were characterized as a synthetic phenotype of the smooth muscle cell with reduced attachment to their surrounding ECM. A biphasic proliferative response of the M-SMC appeared on the second and fifth days. Migration occurred correspondingly in the proliferative period. The populations of M-SMC positive in immunostainings for PDGFs, their receptors, elastase III B, and MMP-1 and MMP-9 also increased biphasically, around 12 h and five days after the injury. The results of these studies suggest that the migrating cells were proliferative and synthesizing PDGFs, elastases, and collagenases.
 ...
PMID:Migration of medial smooth muscle cells to the intima after balloon injury. 918 23

Wound healing is a complex process involving the interactions of many different cell types, matrix components and biological factors, including proteinases and cytokines. This study compared the levels of proteinases (matrix metalloproteinases and plasminogen activators), proteinase inhibitors (tissue inhibitors of metalloproteinases and plasminogen activator inhibitors), inflammatory cytokines and growth factors in acute wound fluid samples collected from the surgical drains of elective breast (n = 24) and colorectal (n = 26) patients on the first postoperative day. Gelatin zymography was used to determine matrix metalloproteinase-2 and -9 levels, quenched fluorescence substrate hydrolysis was applied for total MMP activity and enzyme-linked immunoassays were used to quantitate other factors. Colorectal wound fluid samples showed significantly (p < 0.05) greater levels of the matrix metalloproteinases (MMP-1, 2, 3, and 9), tissue inhibitor of metalloproteinases-1, urokinase plasminogen activator receptor and the inflammatory cytokines (interleukin-1beta, -6, and tumor necrosis factor-alpha); e.g., matrix metalloproteinase-3 colon; median 275 (range 11-2.530) ng/ml; breast; 530-400. However, tissue plasminogen activator and growth factor levels (epidermal growth factor, platelet-derived growth factor, basic fibroblast growth factor, transforming growth factor-beta1) were significantly greater in breast samples; e.g., epidermal growth factor breast 468 (103-1, 444) pg/ml; colon 57(1-573). There was no difference in the levels of urokinase type plasminogen activator, plasminogen activator inhibitor-1 and -2, tissue inhibitor of metalloproteinases -2 or vascular endothelial growth factor. Acute wound fluid from different surgical wounds showed different profiles of proteinases, proteinase inhibitors, and cytokines. This may lead to differences in the rate of tissue remodeling and therefore healing in these two wounds in vivo.
 ...
PMID:Proteinases, their inhibitors, and cytokine profiles in acute wound fluid. 1111 51

We studied the promigratory effect of angiotensin II (ANG II) on cultured bovine retinal microvascular pericytes. ANG II stimulated migration of pericytes by 86% at 10(-8) M, but this effect was lost at 10(-4) M. Migratory responses were inhibited by the ANG II type 1 (AT(1)) receptor antagonist losartan but not by PD-123319, an AT(2) antagonist. Addition of PD-123319 to the 10(-4) M ANG II dose restored migratory responses. The promigratory effect of ANG II (10(-7) M) was reduced by 59% in absence of gradient. Although ANG II augmented the latent matrix metalloproteinase-2 (MMP-2) activity of the pericyte by 35%, it also doubled tissue inhibitors of MMPs. ANG II-induced migration was not altered by a broad-spectrum MMP inhibitor (GM6001); it was inhibited by ~50% by antibodies against transforming growth factor (TGF)-beta(1/2/3) and was abolished by antibodies against platelet-derived growth factor (PDGF)-BB. We conclude that ANG II induces chemotactic responses on retinal microvascular pericytes acting through the AT(1) receptor. This effect is opposed by the AT(2) receptor. ANG II-induced chemotaxis is mediated by PDGF-BB and involves TGF-beta, but it is independent of MMP activity. It is also independent of vascular endothelial growth factor (VEGF) because VEGF did not stimulate pericyte migration. ANG II can contribute to the regulation of retinal neovascularization by stimulating pericyte migration.
 ...
PMID:Angiotensin II stimulates migration of retinal microvascular pericytes: involvement of TGF-beta and PDGF-BB. 1178 25

Platelet-derived growth factor (PDGF)/PDGFRbeta-dependent investment of the vascular endothelium by mural cells (i.e., pericytes and vascular smooth muscle cells; VSMCs) is critical for normal vessel wall structure and function. In the developing vasculature, mural cell recruitment is associated with the functionally undefined expression of the type I transmembrane proteinase, membrane-type 1 matrix metalloproteinase (MT1-MMP). In this paper, using VSMCs and tissues isolated from gene-targeted mice, we identify MT1-MMP as a PDGF-B-selective regulator of PDGFRbeta-dependent signal transduction and mural cell function. In VSMCs, catalytically active MT1-MMP associates with PDGFRbeta in membrane complexes that support the efficient induction of mitogenic signaling by PDGF-B in a matrix metalloproteinase inhibitor-sensitive fashion. In contrast, MT1-MMP-deficient VSMCs display PDGF-B-selective defects in chemotaxis and proliferation as well as ERK1/2 and Akt activation that can be rescued in tandem fashion following retroviral transduction with the wild-type protease. Consistent with these in vitro findings, MT1-MMP-deficient brain tissues display a marked reduction in mural cell density as well as abnormal vessel wall morphology similar to that reported in mice expressing PDGF-B or PDGFRbeta hypomorphic alleles. Together, these data identify MT1-MMP as a novel proteolytic modifier of PDGF-B/PDGFRbeta signal transduction that cooperatively regulates vessel wall architecture in vivo.
 ...
PMID:An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature. 1580 64

Eosinophil cationic proteins influence several biological functions of the respiratory epithelium, yet their direct contribution to airway remodeling has not been established. We show that incubation of the human bronchial epithelial cell line, BEAS-2B, or primary cultured human bronchial epithelial cells, normal human bronchial epithelial cells, with subcytotoxic concentrations (0.1, 0.3, and 1 microM) of major basic protein (MBP), or eosinophil peroxidase (EPO), augmented the transcripts of endothelin-1, TGF-alpha, TGF-beta1, platelet-derived growth factor (PDGF)-beta, epidermal growth factor receptor, metalloproteinase (MMP)-9, fibronectin, and tenascin. A down-regulation of MMP-1 gene expression was observed exclusively in BEAS-2B cells. Cationic protein-induced transcriptional effects were followed by the release of endothelin-1, PDGF-AB in the supernatants by ELISA, and by a down- and up-regulation, respectively, in the levels of MMP-1 and MMP-9 in cell lysates, by Western blot. Cell stimulation with the synthetic polycation, poly-L-arginine, reproduced some but not all effects of MBP and EPO. Finally, simultaneous cell incubation with the polyanion molecules, poly-L-glutamic acid or heparin, restored MMP-1 gene expression but incompletely inhibited MBP- and EPO-induced transcriptional effects as well as endothelin-1 and PDGF-AB release, suggesting that cationic proteins act partially through their cationic charge. We conclude that eosinophil-derived cationic proteins are able to stimulate bronchial epithelium to synthesize factors that influence the number and behavior of structural cells and modify extracellular matrix composition and turnover.
 ...
PMID:Eosinophil-derived cationic proteins activate the synthesis of remodeling factors by airway epithelial cells. 1698 28

The essential etiologic factors of intracranial berry aneurysm may be the hemodynamic stress on the arterial wall. Vascular remodeling triggered by abnormal hemodynamic stress on the blood vessels may play an important role in the formation, development and rupture of intracranial aneurysms. However, the specific causative mechanisms associated with this remain elusive. In this study, we look for the possible mechanism of platelet-derived growth factor B (PDGF-B) on the pathogenesis of saccular aneurysms in rats. Direct microsurgical destruction of the arterial intima and internal elastic lamina at the bifurcation of the carotid artery was performed in 30 rats to induce saccular aneurysms and the contralateral carotid arteries were ligated in half of them. After 4-5 months, the size of the aneurysms was determined. The expressions of PDGF-B and collagen type III on the walls of the normal carotid arteries and the saccular aneurysms were determined by in situ hybridization and immunohistochemistry. Saccular aneurysms could be induced immediately by destroying the intima and internal elastic lamina at the bifurcation of the carotid artery in rats. Saccular aneurysms grew significantly due to the hemodynamic stress in 4-5 months, and much bigger after the ligation of the contralateral carotid artery which enhanced the hemodynamic stress. There was no PDGF-B expression on the walls of the normal carotid arteries in rats, but it was expressed on the aneurysmal walls and more distinctly with the growth of the saccular aneurysms. However, there was collagen type III expression on the media of the normal carotid artery, but its expression decreased on the aneurysmal walls and further reduced with the growth of the saccular aneurysms. So, PDGF-B may induce the expression of MMP for the degradation of collagen type III on the wall of the saccular aneurysms. This may be one of the important mechanisms on the pathogenesis of the saccular aneurysm.
 ...
PMID:Expressions of PDGF-B and collagen type III in the remodeling of experimental saccular aneurysm in rats. 1848 18

Nodular glomerulosclerosis results from increased deposition of extracellular matrix proteins and monotypic light chains. The inability of mesangial cells to degrade abnormal levels of tenascin-C--along with the increased expression of some growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta)--is crucial to the pathogenesis of light chain deposition disease (LCDD). In order to study the molecular processes contributing to LCDD, we grew mesangial cells in three-dimensional matrices and incubated the cells with free light chains purified from the urine of patients with biopsy-proven LCDD, immunoglobulin-associated amyloid deposits, or myeloma cast nephropathy. Light chains of the latter two cohorts served as controls. Mesangial cells incubated with light chains from patients with LCDD show a significant increase in tenascin-C expression, centrally located within newly formed nodules, along with increased expression of PDGF and TGF-betas, compared to mesangial cells incubated with control light chains. There was less extracellular MMP-7 even though its intracellular expression is markedly increased compared to the control. Addition of active MMP-7 degraded this excess tenascin-C in vitro, a process that could be prevented by an exogenous MMP inhibitor. Our in vitro model recapitulates in vivo findings in patients with LCDD, thus allowing definition of the sequential pathologic processes associated with glomerulopathic light chain interactions with mesangial cells.
 ...
PMID:An in vitro model of light chain deposition disease. 1924 79

The majority of patients eligible for periodontal regenerative therapies are aged subjects. Since periodontal ligament cells (PDLC) are essential for periodontal regeneration, the aim of the present study was to determine the effect of cellular aging on PDLC, including genes associated with extracellular matrix metabolism and growth-associated factors. PDLC cultures were obtained from subjects aged 15 to 20 years and subjects aged more than 60 years. Proliferation, cell viability, mineralization assays, and mRNA levels were assessed for type I and III collagen, platelet-derived growth factor (PDGF)-1, basic fibroblast growth factor (bFGF), metalloproteinase (MMP)-2 and-8, and tissue inhibitor of metalloproteinases (TIMP)-1 and-2. Data analysis demonstrated that aging negatively influenced cell proliferation and mineral nodule formation (p < 0.05). Gene expression analysis further showed that mRNA levels for bFGF, PDGF-1, and TIMP-2 were not affected by aging (p > 0.05). In addition, mRNA levels for type I and III collagen were significantly lower in aged cells (p < 0.05), whereas MMP-2 and-8 and TIMP-1 mRNA levels were higher (p < 0.05). Within the limits of the present study, data analysis suggests that aging modulates important biological properties of periodontal ligament cells, diminishes the potential for mineral nodule formation, and favors extracellular matrix degradation.
 ...
PMID:Influence of aging on biological properties of periodontal ligament cells. 1908 40

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


1 2 Next >>