scholarly journals New insights about myofibrillar myopathies: the role of metalloproteinases 2 and 9 in the pathogenesis

2020 ◽  
Author(s):  
Alzira Alves de Siqueira Carvalho ◽  
Vinicius Gomes Silva ◽  
Roseli Corazzini ◽  
Alan Patricio Silva ◽  
Emmanuelle Lacene
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteinases ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Statistical Significance ◽  
Myofibrillar Myopathy ◽  
Type Iv ◽  
Pattern Distribution ◽  
Membrane Methods

Abstract Background There are few reports suggesting that gene expression and activation of various matrix metalloproteinases (MMPs) are deregulated. MMP-2 and MMP-9 represent the two MMPs, which degrade type IV collagen, the component of basement membrane. Methods We analyzed the involvement of gelatinases, MMP-2 and MMP-9, in the pathogenesis of myofibrillar myopathy (MFM). Muscle specimens from 23 patients well diagnosed with MFM, were immunostained by MMP-2 and MMP-9. We analyzed qualitatively the immunoexpression in three compartments: subsarcolemmal (SSC), intracytoplasmic (ICC) and perinuclear (PNC). Results 95,7% and 100% samples showed MMP-2 and MMP-9 upregulation ICC, respectively. PNC showed MMP-2 (82,6%) and MMP-9 (8,7%) regulation (p<0.001). SSC and ICC did not present statistical significance. There was no correlation between mutated gene and immunohistochemical pattern distribution. Conclusion Our results suggest that MMP-2 and/or MMP-9 could participate in the pathomechanism of MFM, causing damage of sarcomere and deposition of protein aggregates.

scholarly journals New insights about myofibrillar myopathies: the role of metalloproteinases 2 and 9 in the pathogenesis

2020 ◽  
Author(s):  
Alzira Alves de Siqueira Carvalho ◽  
Vinicius Gomes Silva ◽  
Roseli Corazzini ◽  
Alan Patricio Silva ◽  
Emmanuelle Lacene
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteinases ◽  
Type Iv Collagen ◽  
Statistical Significance ◽  
Protein Aggregates ◽  
Myofibrillar Myopathy ◽  
Type Iv

Abstract Background There are few reports suggesting that gene expression and activation of various matrix metalloproteinases (MMPs) are deregulated. MMP-2 and MMP-9 represent the two MMPs, which degrade type IV collagen, the component of basement membrane.Methods We analyzed the involvement of gelatinases, MMP-2 and MMP-9, in the pathogenesis of myofibrillar myopathy (MFM). Muscle specimens from 23 patients well diagnosed with MFM, were immunostained by MMP-2 and MMP-9. We analyzed qualitatively the immunoexpression in three compartments: subsarcolemmal (SSC), intracytoplasmic (ICC) and perinuclear (PNC).Results 95,7% and 100% samples showed MMP-2 and MMP-9 upregulation ICC, respectively. PNC showed MMP-2 (82,6%) and MMP-9 (8,7%) regulation (p<0.001). SSC and ICC did not present statistical significance. There was no correlation between mutated gene and immunohistochemical pattern distribution.Conclusion Our results suggest that MMP-2 and/or MMP-9 could participate in the pathomechanism of MFM, causing damage of sarcomere and deposition of protein aggregates.

Epithelial-mesenchymal interactions in the production of basement membrane components in the gut

Development ◽  
1988 ◽  
Vol 102 (2) ◽  
pp. 339-347 ◽  
Author(s):  
P. Simon-Assmann ◽  
F. Bouziges ◽  
C. Arnold ◽  
K. Haffen ◽  
M. Kedinger
Keyword(s):  
Basement Membrane ◽  
Experimental Model ◽  
Type Iv Collagen ◽  
Mesenchymal Cell ◽  
Linear Pattern ◽  
Cellular Origin ◽  
Type Iv ◽  
Species Specific ◽  
Membrane Components

The production and deposition of extracellular matrix proteins and the cellular origin of type-IV collagen have been analysed immunocytochemically in cocultured or transplanted intestinal epithelial-mesenchymal cell associations. In the first experimental model, rat intestinal endodermal cells were cultured on top of confluent monolayers of rat intestinal or skin fibroblastic cells. Under these conditions, interstitial matrix and basement membrane proteins were deposited within the fibroblastic layer over the whole culture period; interactions between the epithelial cells and the fibroblastic cell population, whatever their organ of origin, were required for the production of the basement membrane. In addition, its formation was progressive as assessed by the shift of a spot-like labelling to a continuous linear pattern at the epithelial-mesenchymal interface, and paralleled epithelial cell differentiation. In the second experimental model, chick-rat epithelial-mesenchymal recombinants developed as intracoelomic grafts were used, and the immunocytochemical detection of a basement membrane protein, type-IV collagen, was performed with species-specific antibodies. The major role of the mesenchyme in the deposition of type-IV collagen is supported by the fact that anti-chick but not anti-mammalian antibodies stained this antigen in chick mesenchyme-rat endoderm recombinants. These observations emphasize the role of tissue interactions in the formation of a basement membrane and show that the mesenchymal compartment is the principal endogenous source of type-IV collagen.

Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice

1990 ◽  
Vol 259 (2) ◽  
pp. L47-L52
Author(s):  
D. G. Hoyt ◽  
J. S. Lazo
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Pulmonary Fibrosis ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Subcutaneous Infusion ◽  
Type Iv ◽  
Steady State Levels ◽  
Membrane Components ◽  
Basement Membrane Components

Constant 7-day subcutaneous infusion of bleomycin (100 mg/kg) induces pulmonary fibrosis in C57Bl/6N mice, whereas BALB/cN mice are relatively resistant. In contrast, cyclophosphamide (200 mg/kg, ip) induces fibrosis in BALB/cN mice, whereas C57Bl/6N mice are resistant. The effect of these drugs on the pulmonary levels of mRNA encoding the major basement membrane components, laminin and type IV collagen, relative to poly (A+)RNA was determined in both C57Bl/6N and BALB/cN mice. In the sensitive C57Bl/6N mice, bleomycin increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the absence of increases in laminin A, B1, and B2 mRNA/poly (A+)RNA. In the relatively resistant BALB/cN mice, bleomycin did not alter alpha 1IV procollagen mRNA/poly (A+)RNA and only transiently increased laminin A, B1, B2, and alpha 2IV procollagen mRNA/poly (A+)RNA. Similarly, cyclophosphamide increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the sensitive BALB/cN mice and not in C57Bl/6N mice. Laminin mRNAs/poly (A+)RNA were not increased by cyclophosphamide in either strain. Thus, in these models, pulmonary fibrosis is preceded by a coordinate increase in steady-state levels of mRNA encoding basement membrane procollagen but is not associated with an increase in laminin gene expression

Role of 17 β-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall

2007 ◽  
Vol 18 (10) ◽  
pp. 1185-1190 ◽  
Author(s):  
Rogerio de Fraga ◽  
Miriam Dambros ◽  
Ricardo Miyaoka ◽  
Cássio Luís Zanettini Riccetto ◽  
Paulo César Rodrigues Palma
Keyword(s):  
Basement Membrane ◽  
Type Iv Collagen ◽  
Bladder Wall ◽  
Collagen Fibers ◽  
Volumetric Density ◽  
Type Iv

scholarly journals Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yuexin Wu ◽  
Yuyan Cao ◽  
Keren Xu ◽  
Yue Zhu ◽  
Yuemei Qiao ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Patient Survival ◽  
Early Stage ◽  
Ecm Remodeling ◽  
Type Iv ◽  
Ecm Proteins ◽  
Stage Disease ◽  
Cirrhotic Patients

AbstractLiver cirrhosis remains major health problem. Despite the progress in diagnosis of asymptomatic early-stage cirrhosis, prognostic biomarkers are needed to identify cirrhotic patients at high risk developing advanced stage disease. Liver cirrhosis is the result of deregulated wound healing and is featured by aberrant extracellular matrix (ECM) remodeling. However, it is not comprehensively understood how ECM is dynamically remodeled in the progressive development of liver cirrhosis. It is yet unknown whether ECM signature is of predictive value in determining prognosis of early-stage liver cirrhosis. In this study, we systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis. In particular, basement membrane (BM) was heavily deposited at the fibrogenesis stage. BM component minor type IV collagen α5 chain expression was increased in activated hepatic stellate cells. Knockout of minor type IV collagen α5 chain ameliorated liver fibrosis by hampering hepatic stellate cell activation and promoting hepatocyte proliferation. ECM signatures were differentially enriched in the biopsies of good and poor prognosis early-stage liver cirrhosis patients. Clusters of ECM proteins responsible for homeostatic remodeling and tissue fibrogenesis, as well as basement membrane signature were significantly associated with disease progression and patient survival. In particular, a 14-gene signature consisting of basement membrane proteins is potent in predicting disease progression and patient survival. Thus, the ECM signatures are potential prognostic biomarkers to identify cirrhotic patients at high risk developing advanced stage disease.

Isolation and characterization of pepsin-solubilized human basement membrane (type IV) collagen peptides

Biochemistry ◽  
1983 ◽  
Vol 22 (21) ◽  
pp. 4940-4948 ◽  
Author(s):  
Robert S. MacWright ◽  
Virginia A. Benson ◽  
Katherine T. Lovello ◽  
Michel Van der Rest ◽  
Peter P. Fietzek
Keyword(s):  
Basement Membrane ◽  
Type Iv Collagen ◽  
Collagen Peptides ◽  
Type Iv ◽  
Isolation And Characterization ◽  
Membrane Type
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