scholarly journals Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination of Borrelia burgdorferi

2009 ◽  
Vol 77 (7) ◽  
pp. 2643-2649 ◽  
Author(s):  
Andrew J. Heilpern ◽  
Warren Wertheim ◽  
Jia He ◽  
George Perides ◽  
Roderick T. Bronson ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Insertion Site ◽  
Matrix Metalloproteinase 9 ◽  
Lyme Arthritis ◽  
Type I ◽  
Wild Type ◽  
Tissue Destruction ◽  
Metalloproteinase 9

ABSTRACT Borrelia burgdorferi, the causative agent of Lyme arthritis, does not produce any exported proteases capable of degrading extracellular matrix despite the fact that it is able to disseminate from a skin insertion site to infect multiple organs. Prior studies have shown that B. burgdorferi induces the host protease, matrix metalloproteinase 9 (MMP-9), and suggested that the induction of MMP-9 may allow the organism to disseminate and produce local tissue destruction. We examined the role of MMP-9 in dissemination of B. burgdorferi and pathogenesis of Lyme arthritis. In a MMP-9−/− mouse model, MMP-9 was not required for the dissemination of the spirochete to distant sites. However, MMP-9−/− exhibited significantly decreased arthritis compared to wild-type mice. The decrease in arthritis was not due to an inability to control infection since the spirochete numbers in the joints were identical. Levels of inflammatory chemokines and cytokines were also similar in MMP-9−/− and wild-type mice. We examined whether decreased inflammation in MMP-9−/− mice may be the result of decreased production of neoattractants by MMP-9-dependent cleavage of collagen. MMP-9 cleavage of type I collagen results in increased monocyte chemoattraction. MMP-9 plays an important role in regulating inflammation in Lyme arthritis, potentially through the cleavage of type I collagen.

scholarly journals Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0244650
Author(s):  
Maha Sabry ◽  
Seham Mostafa ◽  
Laila Rashed ◽  
Marwa Abdelgwad ◽  
Samaa Kamar ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
High Fat Diet ◽  
Inflammatory Markers ◽  
Type I Collagen ◽  
Bone Diseases ◽  
Matrix Metalloproteinase 9 ◽  
Type I ◽  
High Fat ◽  
Major Player ◽  
Metalloproteinase 9

Background Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. On the other hand, the relationship between bone diseases and obesity remains unclear. An increasing number of biological and epidemiological studies suggest the presence of a link between atherosclerosis and osteoporosis, however, the precise molecular pathways underlying this close association remain poorly understood. The present work thus aimed to study Matrix Metalloproteinase 9 (MMP-9), as a proposed link between atherosclerosis and osteoporosis in high fat diet fed rats. Methods and findings 40 rats were randomly divided into 4 groups: control, untreated atherosclerosis group, atherosclerotic rats treated with carvedilol (10mg/kg/d) and atherosclerotic rats treated with alendronate sodium (10mg/kg/d). After 8 weeks, blood samples were collected for estimation of Lipid profile (Total cholesterol, HDL, TGs), inflammatory markers (IL-6, TNF-α, CRP and NO) and Bone turnover markers (BTMs) (Alkaline phosphatase, osteocalcin and pyridinoline). Rats were then euthanized and the aortas and tibias were dissected for histological examination and estimation of MMP-9, N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX) and NF-kB expression. Induction of atherosclerosis via high fat diet and chronic stress induced a significant increase in BTMs, inflammatory markers and resulted in a state of dyslipidaemia. MMP-9 has also shown to be significantly increased in the untreated atherosclerosis rats and showed a significant correlation with all measured parameters. Interestingly, Carvedilol and bisphosphonate had almost equal effects restoring the measured parameters back to normal, partially or completely. Conclusion MMP-9 is a pivotal molecule that impact the atherogenic environment of the vessel wall. A strong cross talk exists between MMP-9, cytokine production and macrophage function. It also plays an important regulatory role in osteoclastogenesis. So, it may be a key molecule in charge for coupling CVD and bone diseases in high fat diet fed rats. Therefore, we suggest MMP-9 as a worthy molecule to be targeted pharmacologically in order to control both conditions simultaneously. Further studies are needed to support, to invest and to translate this hypothesis into clinical studies and guidelines.

Solubilization of type I collagen from fish muscle connective tissue by matrix metalloproteinase-9 at chilled temperature

2003 ◽  
Vol 69 (5) ◽  
pp. 1053-1059 ◽  
Author(s):  
Mitsutoshi KUBOTA ◽  
Masato KINOSHITA ◽  
Kazuharu TAKEUCHI ◽  
Satoshi KUBOTA ◽  
Haruhiko TOYOHARA ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Fish Muscle ◽  
Matrix Metalloproteinase 9 ◽  
Type I ◽  
Metalloproteinase 9

scholarly journals Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels

2014 ◽  
Vol 306 (11) ◽  
pp. L1006-L1015 ◽  
Author(s):  
Tetsu Kobayashi ◽  
HuiJung Kim ◽  
Xiangde Liu ◽  
Hisatoshi Sugiura ◽  
Tadashi Kohyama ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Human Fibroblasts ◽  
Matrix Metalloproteinase 9 ◽  
Lung Fibroblasts ◽  
Type I ◽  
Image Analysis System ◽  
Collagen Gels ◽  
3D Collagen ◽  
Metalloproteinase 9 ◽  
Tgf Β1

Matrix metalloproteinase-9 (MMP-9) is a matrix-degrading enzyme implicated in many biological processes, including inflammation. It is produced by many cells, including fibroblasts. When cultured in three-dimensional (3D) collagen gels, fibroblasts contract the surrounding matrix, a function that is thought to model the contraction that characterizes both normal wound repair and fibrosis. The current study was designed to evaluate the role of endogenously produced MMP-9 in fibroblast contraction of 3D collagen gels. Fibroblasts from mice lacking expression of MMP-9 and human lung fibroblasts (HFL-1) transfected with MMP-9 small-interfering RNA (siRNA) were used. Fibroblasts were cast into type I collagen gels and floated in culture medium with or without transforming growth factor (TGF)-β1 for 5 days. Gel size was determined daily using an image analysis system. Gels made from MMP-9 siRNA-treated human fibroblasts contracted less than control fibroblasts, as did fibroblasts incubated with a nonspecific MMP inhibitor. Similarly, fibroblasts cultured from MMP-9-deficient mice contracted gels less than did fibroblasts from control mice. Transfection of the MMP-9-deficient murine fibroblasts with a vector expressing murine MMP-9 restored contractile activity to MMP-9-deficient fibroblasts. Inhibition of MMP-9 reduced active TGF-β1 and reduced several TGF-β1-driven responses, including activity of a Smad3 reporter gene and production of fibronectin. Because TGF-β1 also drives fibroblast gel contraction, this suggests the mechanism for MMP-9 regulation of contraction is through the generation of active TGF-β1. This study provides direct evidence that endogenously produced MMP-9 has a role in regulation of tissue contraction of 3D collagen gels mediated by fibroblasts.

Leukocyte matrix metalloproteinase-9 is elevated and contributes to lymphocyte activation in type I diabetes

2005 ◽  
Vol 37 (11) ◽  
pp. 2406-2416 ◽  
Author(s):  
Meilang Xue ◽  
Patrick J. Thompson ◽  
Rory Clifton-Bligh ◽  
Greg Fulcher ◽  
Eileen D.M. Gallery ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Diabetes ◽  
Lymphocyte Activation ◽  
Matrix Metalloproteinase 9 ◽  
Type I ◽  
Metalloproteinase 9

scholarly journals CD14 Mediates Cross Talk between Mononuclear Cells and Fibroblasts for Upregulation of Matrix Metalloproteinase 9 by Borrelia burgdorferi

2007 ◽  
Vol 75 (6) ◽  
pp. 3062-3069 ◽  
Author(s):  
Zhihui Zhao ◽  
Rhonda Fleming ◽  
Bilaal McCloud ◽  
Mark S. Klempner
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Matrix Metalloproteinase ◽  
Mononuclear Cells ◽  
Erythema Migrans ◽  
Matrix Metalloproteinase 9 ◽  
Dependent Manner ◽  
U937 Cells ◽  
Concentration Dependent Manner ◽  
Metalloproteinase 9

ABSTRACT Lyme disease is an infection caused by a tick-borne spirochete, Borrelia burgdorferi. Matrix metalloproteinase 9 (MMP-9) was selectively upregulated in the erythema migrans skin lesions of patients with acute Lyme disease. In this study, the mechanism of upregulation of MMP-9 was investigated in vitro and in vivo. The concentrations of MMP-9 and soluble CD14 were markedly elevated in serum from patients with acute Lyme disease and were also upregulated in U937 cells by B. burgdorferi in a time- and concentration-dependent manner. MMP-9 mRNA was expressed at baseline in fibroblasts in the presence or absence of B. burgdorferi. However, when fibroblasts were incubated with supernatants from U937 cells with B. burgdorferi or recombinant CD14, the expression of MMP-9 was significantly increased. This effect was completely abolished by the anti-CD14 antibody. These data suggest that the upregulation of MMP-9 by B. burgdorferi involves the CD14 pathway in infiltrating inflammatory cells. Fibroblasts could be recruited to amplify local production of MMP-9 by acquiring CD14 from macrophages.

Abstract 166: Matrix Metalloproteinase-9 Mediates Post-hypoxic Vascular Pruning Of Cerebral Blood Vessels By Degrading Laminin And Claudin-5

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Amin Boroujerdi ◽  
Jennifer V Welser-Alves ◽  
Richard Milner
Keyword(s):  
Matrix Metalloproteinase ◽  
Tight Junction ◽  
Blood Vessels ◽  
Matrix Metalloproteinase 9 ◽  
Vascular Density ◽  
Cerebral Blood Vessels ◽  
Wild Type ◽  
Junction Protein ◽  
Metalloproteinase 9

Objective: Vascular remodeling involves a highly coordinated break-down and build-up of the vascular basal lamina and inter-endothelial tight junction proteins. The goal of this study was to examine the role of matrix metalloproteinase-9 (MMP-9) in remodeling of cerebral blood vessels, both in hypoxia-induced angiogenesis and in the vascular pruning that accompanies the switch from hypoxia back to normoxia. Approach and Results: In a chronic mild hypoxia model of cerebrovascular remodeling, gel zymography revealed that MMP-9 levels were increased, both in the hypoxic angiogenic response and in the post-hypoxic pruning response. Compared to wild-type mice, MMP-9 KO mice showed no alteration in hypoxic-induced angiogenesis, but did show marked delay in post-hypoxic vascular pruning. In wild-type mice, vascular pruning was associated with fragmentation of vascular laminin and the tight junction protein claudin-5, while this process was markedly attenuated in MMP-9 KO mice. In vitro experiments showed that hypoxia stimulated MMP-9 expression in brain endothelial cells (BECs) but not pericytes. While immunofluorescent and flow cytometry analyses showed that hypoxia led to reduced expression of laminin and claudin-5 in wild-type BECs, this decrease was absent in MMP-9 KO BECs. Conclusions: These results show that while MMP-9 is not essential for hypoxic-induced cerebral angiogenesis, it plays an important role in post-hypoxic vascular pruning by degrading laminin and claudin-5. Our data support the concept that MMP-9 inhibition might provide therapeutic benefit in the treatment of ischemic stroke, by preventing post-hypoxic vascular pruning, thereby optimizing vascular density and integrity.

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