scholarly journals Malignant Fibrous Histiocytoma, Aggressive Fibromatosis and Benign Fibrous Tumors Express mRNA for the Metalloproteinase InducerEMMPRINand the MetalloproteinasesMMP-2andMT1-MMP

Sarcoma ◽  
2001 ◽  
Vol 5 (3) ◽  
pp. 143-149 ◽  
Author(s):  
Jan Åhlén ◽  
Ulla Enberg ◽  
Catharina Larsson ◽  
Olle Larsson ◽  
Tony Frisk ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Mrna Expression ◽  
Proteolytic Enzymes ◽  
Aggressive Fibromatosis ◽  
Matrix Metalloproteinase 2 ◽  
Hybridization Technique ◽  
Mrna Levels ◽  
Mesenchymal Tumors ◽  
Membrane Type

Purpose:Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to stimulate fibroblasts to production of matrix metalloproteinases (MMPs). MMPs comprise a family of proteolytic enzymes implicated in the degradation of extracellular matrix which has been proposed to be one of the essential steps in tumor invasion and metastases. In the present study we investigated the expression and location of mRNAs forEMMPRIN, matrix metalloproteinase-2 (MMP-2), and membrane-type 1 matrix metalloproteinase (MT1-MMP) in mesenchymal tumors with different tendencies to recur or metastasize.Subjects:Eight malignant fibrous histiocytomas (MFH), seven aggressive fibromatosis (AF), and six benign fibrous tumors (BF).Method:The mRNA-expression ofEMMPRIN,MMP-2andMT1-MMPwere studied using mRNAin situhybridization technique.Results:The mRNA-expression ofEMMPRIN,MMP-2andMT1-MMPrespectively were found at varying frequency and level in all tumor types. The mRNAs corresponding toEMMPRINandMMP-2were seen in neoplastic cells as well as in endothelial cells both inside and outside the tumor pseudo-capsule, whereasMT1-MMPwas seen only within the tumors. The estimated mRNA levels ofEMMPRINandMMP-2covariated significantly. Overall, the highest expression was found in the MFH tumors and the lowest levels in the BF tumors.Discussion:These findings suggest that the MMP-inducerEMMPRINand the extracellular matrix degrading system involving the metalloproteinasesMMP-2andMT1-MMPis frequently activated in mesenchymal tumors. The covariation betweenEMMPRINandMMP-2support previous findings that EMMPRIN may be an inducer of MMP-2. The high levels ofMMP-2mRNA in MFH indicate a relationship between the proteolytic activity ofMMP-2and the tumor aggressiveness.

scholarly journals Expression profile of microRNA-29b and its action on matrix metalloproteinase 2 (MMP-2) in the cervical carcinogenic process

2021 ◽  
Vol 10 (11) ◽  
pp. e372101119471
Author(s):  
Giwellington Silva Albuquerque ◽  
Renata Santos de Oliveira ◽  
Jônatas André da Silva Santos ◽  
Miquéias Pereira Lima do Amaral ◽  
Juliana Maria de Souza ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Real Time Pcr ◽  
Proteolytic Enzymes ◽  
Matrix Metalloproteinase 2 ◽  
Cervical Cancers ◽  
Common Cancer ◽  
Direct Association ◽  
Carcinogenic Process

Background: Cervical cancer is the fourth most common cancer among women worldwide. In order to make the diagnosis earlier and more accurate, increase the prospect of using microRNA-29b, which targets matrix metalloproteinase-2 (MMP-2), proteolytic enzymes that play a significant role in the degradation of the important extracellular matrix in progression of cervical carcinogenic lesions. Objectives: The aim of this study was to evaluate the levels of expression of microRNA-29b at all histological levels of carcinogenesis and its relationship with MMP-2 in this type of cancer. Methods: RNA was extracted from eighteen paraffin-embedded biopsy samples diagnosed with carcinoma and 19 considerable healthy samples, after which a real-time PCR technician was performed for expression analysis. Results: Our results show underexpression of microRNA-29b and MMP-2. This decrease in expression was statistically significant and differentiated in the histopathological subtypes. In addition, it has been shown that MMP-2 is directly regulated by microRNA-29b. No other studies were found that performed the same analysis on cervical cancers. Conclusion: Our results indicate a potential diagnosis of microRNA-29b and MMP-2 for lesions and cervical cancer, and show a direct association between these molecules.

scholarly journals Enhanced expression of membrane type-1 matrix metalloproteinase in mesangial proliferative glomerulonephritis.

1998 ◽  
Vol 9 (12) ◽  
pp. 2262-2271 ◽  
Author(s):  
K Hayashi ◽  
S Osada ◽  
K Shofuda ◽  
S Horikoshi ◽  
I Shirato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteinase ◽  
Mrna Expression ◽  
Reverse Transcription ◽  
Matrix Metalloproteinase 2 ◽  
Phenotypic Change ◽  
Similar Distribution ◽  
Glomerular Diseases ◽  
Reverse Transcription Pcr ◽  
Membrane Type

Matrix metalloproteinase-2 (MMP-2, gelatinase A) is involved in the inflammatory and sclerotic events of glomerular diseases. Newly identified membrane-type matrix metalloproteinases (MT-MMP) have been shown to activate specifically proMMP-2. To date, several types of MT-MMP have been cloned; however, their expressions in glomerular diseases have not been evaluated. To investigate the role of MT-MMP in glomerular diseases, the glomerular gene expression and enzymatic activity of MT-MMP were examined during the time course of nephritis induced in rats by anti-Thy1.1 antibody injection. Both MT1-MMP and MMP-2 mRNA expression increased prominently 5 and 10 d after anti-Thy1.1 antibody injection and decreased thereafter, as assayed by semiquantitative reverse transcription-PCR. In contrast, there were no remarkable changes in the gene expression of MT2-MMP between normal and diseased tissue, and that of MT3-MMP was not detected in isolated glomeruli by reverse transcription-PCR analysis. The activation of proMMP-2 as analyzed by gelatin zymography correlated with the glomerular MT1-MMP gene expression, suggesting that proMMP-2 was activated by MT1-MMP. Protein and mRNA expression of fibronectin, one of the major mesangial matrix proteins and substrate of MMP-2, were also synchronized with MT1-MMP and MMP-2 expression. In situ hybridization revealed intense MT1-MMP mRNA expression in the proliferating mesangial cells. Interestingly, MT1-MMP gene expression exhibited a similar distribution as alpha-smooth muscle actin expression, which was closely associated with mesangial phenotypic change. These results suggest that among the newly identified MT-MMP, MT1-MMP may play the central role in activation of proMMP-2. Furthermore, the enhancement of MT1-MMP and MMP-2 expression associated with mesangial phenotypic change may contribute to the development of anti-Thy1.1 antibody-induced glomerulonephritis and remodeling of extracellular matrices.

Induction of matrix metalloproteinase-2 enhances systemic arterial contraction after hypoxia

2007 ◽  
Vol 292 (1) ◽  
pp. H684-H693 ◽  
Author(s):  
Jeff Z. He ◽  
Adrian Quan ◽  
Yi Xu ◽  
Hwee Teoh ◽  
Guilin Wang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Systemic Circulation ◽  
Mesenteric Arteries ◽  
Matrix Metalloproteinase 2 ◽  
Organ Bath ◽  
Mrna Levels ◽  
Resistance Arteries ◽  
Protein Levels ◽  
Arterial Contraction ◽  
Membrane Type

This study was carried out to determine the role of increased vascular matrix metalloproteinase-2 (MMP-2) expression in the changes in systemic arterial contraction after prolonged hypoxia. Rats and mice were exposed to hypoxia (10% and 8% O2, respectively) or normoxia (21% O2) for 16 h, 48 h, or 7 days. Aortae and mesenteric arteries were either mounted in organ bath myographs or frozen in liquid nitrogen. MMP-2 inhibition with cyclic CTTHWGFTLC (CTT) reduced contraction to phenylephrine (PE) in aortae and mesenteric arteries from rats exposed to hypoxia for 7 days but not in vessels from normoxic rats. Similarly, CTT reduced contraction to Big endothelin-1 (Big ET-1) in aortae from rats exposed to hypoxia for 7 days. Responses to PE were reduced in hypoxic MMP-2−/− mice compared with MMP-2+/+ mice. Increased contraction to Big ET-1 after hypoxia was observed in MMP-2+/+ mice but not in MMP-2−/− mice. Rat aortic MMP-2 and membrane type 1 (MT1)-MMP protein levels and MMP activity were increased after 7 days of hypoxia. Rat aortic MMP-2 and MT1-MMP mRNA levels were increased in the deep medial vascular smooth muscle. We conclude that hypoxic induction of MMP-2 expression potentiates contraction in systemic conduit and resistance arteries. This may preserve the capacity to regulate the systemic circulation in the transition between the alterations in vascular tone and structural remodeling that occurs during prolonged hypoxic epochs.

scholarly journals High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions

2009 ◽  
Vol 78 (3) ◽  
pp. 1012-1021 ◽  
Author(s):  
Rosane M. B. Teles ◽  
Rose B. Teles ◽  
Thais P. Amadeu ◽  
Danielle F. Moura ◽  
Leila Mendonça-Lima ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cultured Cells ◽  
Leukocyte Migration ◽  
Therapeutic Interventions ◽  
Matrix Metalloproteinase 2 ◽  
Mrna Levels ◽  
Membrane Breakdown ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-α. It was observed that IFN-γ, TNF-α, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-α, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.

scholarly journals Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Sprouting Angiogenesis ◽  
Sphingosine 1 Phosphate ◽  
Wall Shear ◽  
Membrane Type

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.

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