Modulation of matrix metalloproteinase-9 in hepatic stellate cells by three-dimensional type I collagen: its activation and signaling pathway

The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis duringBrucella abortusinfection. This study assessed the role of BPE005 protein fromB. abortusin the fibrotic phenotype induced on hepatic stellate cells duringB. abortusinfectionin vitroandin vivo. We demonstrated that the fibrotic phenotype induced byB. abortuson hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB fromB. abortus. Our results indicated thatB. abortusinhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate thatB. abortustilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway.

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Reciprocal Modulation of Matrix Metalloproteinase-13 and Type I Collagen Genes in Rat Hepatic Stellate Cells

American Journal Of Pathology ◽

10.1016/s0002-9440(10)64312-x ◽

2003 ◽

Vol 162 (6) ◽

pp. 1771-1780 ◽

Cited By ~ 37

Author(s):

Benjamin Schaefer ◽

Ana María Rivas-Estilla ◽

Noemí Meraz-Cruz ◽

Miguel Arturo Reyes-Romero ◽

Zamira H. Hernández-Nazara ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Hepatic Stellate Cells ◽

Type I Collagen ◽

Stellate Cells ◽

Type I ◽

Matrix Metalloproteinase 13 ◽

Collagen Genes

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

Infection and Immunity ◽

10.1128/iai.00214-09 ◽

2009 ◽

Vol 77 (7) ◽

pp. 2643-2649 ◽

Cited By ~ 30

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.

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Contribution of hepatic stellate cells and matrix metalloproteinase 9 in acute liver failure

Liver International ◽

10.1111/j.1478-3231.2008.01775.x ◽

2008 ◽

Vol 28 (7) ◽

pp. 959-971 ◽

Cited By ~ 31

Author(s):

Chunli Yan ◽

Ling Zhou ◽

Yuan-Ping Han

Keyword(s):

Matrix Metalloproteinase ◽

Liver Failure ◽

Acute Liver Failure ◽

Hepatic Stellate Cells ◽

Stellate Cells ◽

Matrix Metalloproteinase 9 ◽

Metalloproteinase 9

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

PLoS ONE ◽

10.1371/journal.pone.0244650 ◽

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.

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