Matrix Metalloproteinase-9 is Involved in the Fibrotic Process in Denervated Muscles after Sciatic Nerve Trauma and Recovery

AbstractFibrosis of the injured muscles is a problem of recovery from trauma and denervation. The aim of the work was to investigate the interconnection of matrix metalloproteinase-9 (ММР-9) activity in denervated muscles with fibrosis and to estimate its role in nerve restoration by the epineurial suture, fibrin-based glue, and polyethylene glycol hydrogel. The activity of matrix metalloproteinases was estimated by gelatin zymography. Collagen density in muscles was determined histochemically. An increased level of the active MMP-9 is associated with the fibrous changes in the denervated skeletal muscles and after an epineurial suture. The use of fibrin glue and polyethylene glycol hydrogel resulted in a lower level of collagen and ММР-9 activity, which may be a therapeutic target in the treatment of neuromuscular lesions, and has value in fibrosis analysis following microsurgical intervention for peripheral nerve reconstruction.

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Matrix metalloproteinase-9 expression in folliculostellate cells of rat anterior pituitary gland

Journal of Endocrinology ◽

10.1530/joe-11-0433 ◽

2011 ◽

Vol 212 (3) ◽

pp. 363-370 ◽

Cited By ~ 8

Author(s):

Cimi Ilmiawati ◽

Kotaro Horiguchi ◽

Ken Fujiwara ◽

Takashi Yashiro

Keyword(s):

Matrix Metalloproteinase ◽

Pituitary Gland ◽

Anterior Pituitary ◽

Fluorescent Protein ◽

Gelatin Zymography ◽

Matrix Metalloproteinase 9 ◽

Anterior Pituitary Gland ◽

Rt Pcr ◽

Metalloproteinase 9

Folliculostellate (FS) cells of the anterior pituitary gland express a variety of regulatory molecules. Using transgenic rats that express green fluorescent protein specifically in FS cells, we recently demonstrated that FS cells in vitro showed marked changes in motility, proliferation, and that formation of cellular interconnections in the presence of laminin, a component of the extracellular matrix, closely resembled those observed in vivo. These findings suggested that FS cells express matrix metalloproteinase-9 (MMP-9), which assists their function on laminin. In the present study, we investigate MMP-9 expression in rat anterior pituitary gland and examine its role in motility and proliferation of FS cells on laminin. Immunohistochemistry, RT-PCR, immunoblotting, and gelatin zymography were performed to assess MMP-9 expression in the anterior pituitary gland and cultured FS cells. Real-time RT-PCR was used to quantify MMP-9 expression in cultured FS cells under different conditions and treatments. MMP-9 expression was inhibited by pharmacological inhibitor or downregulated by siRNA and time-lapse images were acquired. A 5-bromo-2′-deoxyuridine assay was performed to analyze the proliferation of FS cells. Our results showed that MMP-9 was expressed in FS cells, that this expression was upregulated by laminin, and that laminin induced MMP-9 secretion by FS cells. MMP-9 inhibition and downregulation did not impair FS motility; however, it did impair the capacity of FS cells to form interconnections and it significantly inhibited proliferation of FS cells on laminin. We conclude that MMP-9 is necessary in FS cell interconnection and proliferation in the presence of laminin.

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Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis

Disease Markers ◽

10.1155/2015/138974 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Ming-Fa Liu ◽

Yong-Yang Hu ◽

Tao Jin ◽

Ke Xu ◽

Shao-Hong Wang ◽

...

Keyword(s):

Brain Tumors ◽

Matrix Metalloproteinase ◽

Gelatin Zymography ◽

Matrix Metalloproteinase 9 ◽

Urine Samples ◽

Complex Activity ◽

Clinical Prognosis ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase ◽

Metalloproteinase 9

Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT) and preoperative urine samples (Preop-1d urine). Activity was reduced by seven days after surgery (Postop-1w urine) and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients.

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Abstract 3646: Oxidative Stress-Mediated Thombospondin-2 Upregulation Contributes to Diabetic Endothelial Progenitor Cell Dysfunction via Matrix Metalloproteinase-9 Activation

Circulation ◽

10.1161/circ.118.suppl_18.s_457-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Ok-Nam Bae ◽

Alex F Chen

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Matrix Metalloproteinase ◽

Vascular Complications ◽

Gelatin Zymography ◽

Matrix Metalloproteinase 9 ◽

Endothelial Progenitor ◽

Qrt Pcr ◽

Metalloproteinase 9

Endothelial progenitor cells (EPCs) play an essential role in angiogenesis but are dysfunctional in diabetes featuring excessive oxidative stress. Thrombospondin-2 (TSP-2) and matrix metalloproteinase-9 (MMP-9) possess potent anti-angiogenic properties, but their roles on EPC dysfunction in diabetes remain unknown. We tested the hypothesis that increased oxidative stress up-regulates TSP-2 and contributes to diabetic EPC dysfunction through MMP-9 activation in type 2 diabetes. Bone marrow-derived EPCs from adult male type 2 diabetic db/db mice (C57BLKS/J, 9 –13 weeks) and control db/+ mice on the same genetic background were used (blood glucose level, 451.0±8.2 mg/dL for db/db, n=38, vs. 141.3±3.7 mg/dL for db/+, n=28, p<0.01). TSP-2 mRNA and protein were both up-regulated in diabetic EPCs (3.43±0.41 folds of mRNA by qRT-PCR, n=6, p<0.01; 2.35±0.16 folds of protein by Western blot analysis, n= 5, p<0.01, vs. db/+). Silencing TSP-2 by its siRNA in diabetic EPCs improved their angiogenesis in vitro (Matrigel tube formation assay, n=4, p<0.05 vs. scrambled RNA). The increase of TSP-2 in diabetic EPCs was reversed by adenoviral vector-mediated overexpression of dominant-negative Rac1 (68±9%, n=5, p<0.05 vs. β-galactosidase reporter gene), which retards endogenous NADPH oxidase subunit Rac1 activity. Furthermore, both MMP-9 mRNA and enzymatic activity were significantly increased in diabetic EPCs (6.42±2.46 folds of mRNA by qRT-PCR, n=6, p<0.01; 1.37±0.08 folds activity by gelatin zymography, n=3, p<0.01, vs. db/+). The increased MMP-9 activity was significantly inhibited by silencing TSP-2 by its siRNA in diabetic EPCs (47±15%, n=5, p<0.05 vs. scrambled RNA). Our results suggest that up-regulation of TSP-2 mediated by increased oxidative stress contributes to dysfunction of EPC angiogenesis through MMP-9 activation in type 2 diabetes. These findings may provide a basis of targeting oxidative stress/TSP-2/MMP-9 pathway for restoring EPC angiogenic function and cell therapy of diabetic vascular complications.

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