scholarly journals Homocysteine and Hypertension in Diabetes: Does PPARγHave a Regulatory Role?

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Utpal Sen ◽  
Suresh C. Tyagi
Keyword(s):  
Matrix Protein ◽  
Vascular Endothelial Cells ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Extracellular Matrix Protein ◽  
Matrix Remodeling ◽  
Renal Volume ◽  
Vascular Effects ◽  
Beneficial Effects ◽  
The Matrix ◽  
Volume Retention

Dysfunction of macro- and microvessels is a major cause of morbidity and mortality in patients with cardio-renovascular diseases such as atherosclerosis, hypertension, and diabetes. Renal failure and impairment of renal function due to vasoconstriction of the glomerular arteriole in diabetic nephropathy leads to renal volume retention and increase in plasma homocysteine level. Homocysteine, which is a nonprotein amino acid, at elevated levels is an independent cardio-renovascular risk factor. Homocysteine induces oxidative injury of vascular endothelial cells, involved in matrix remodeling through modulation of the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) axis, and increased formation and accumulation of extracellular matrix protein, such as collagen. In heart this leads to increased endothelial-myocyte uncoupling resulting in diastolic dysfunction and hypertension. In the kidney, increased matrix accumulation in the glomerulus causes glomerulosclerosis resulting in hypofiltration, increased renal volume retention, and hypertension. PPARγagonist reduces tissue homocysteine levels and is reported to ameliorate homocysteine-induced deleterious vascular effects in diabetes. This review, in light of current information, focuses on the beneficial effects of PPARγagonist in homocysteine-associated hypertension and vascular remodeling in diabetes.

scholarly journals Myrcene exerts anti-asthmatic activity in neonatal rats via modulating the matrix remodeling

2020 ◽  
Vol 34 ◽  
pp. 205873842095494
Author(s):  
Yanhui Du ◽  
Jie Luan ◽  
Ren Peng Jiang ◽  
Juan Liu ◽  
Yan Ma
Keyword(s):  
Matrix Protein ◽  
Antioxidant Properties ◽  
Experimental Period ◽  
Specific Ige ◽  
Protective Role ◽  
Extracellular Matrix Protein ◽  
Matrix Remodeling ◽  
Cell Counts ◽  
Cytokine Analysis ◽  
The Matrix

Myrcene (MC), an organic hydrocarbon, was found to exert anti-inflammatory, analgesic, antimutagenic and antioxidant properties. However, the protective role of MC has not been reported against neonatal asthma. Wistar rats induced with asthma were administered with MC; while asthma control and vehicle control were maintained without MC administration. At the end of the experimental period, lung histology, inflammatory cell counts, cytokine analysis, matrix protein expressions were elucidated. Rats administered with MC exerted significant ( P < 0.05) defense in protecting the lung tissue with the evidenced restoration of alveolar thickening of the lung tissues. Also, the present study elicited the anti-asthmatic activity of MC, especially via modulating the extracellular matrix protein expression in the asthma-induced animals, while a significant reduction ( P < 0.05) in the fibrotic markers were found in MC treated animals. Moreover, the protective effect of MC was evidenced with reduced leukocyte infiltration in BALF, hypersensitive specific IgE levels with a profound decrease in the inflammatory cytokines such as IL-2, IL-4, IL-18, and IL-21 in MC administered animals compared to the asthma-induced group. To an extent, the markers of asthmatic inflammation such as CD14, MCP-1, and TARC were also found to be attenuated in MC exposed animals. The possible application of MC is a promising drug for the treatment of asthma-mediated complications.

scholarly journals Poly-L-Lysine and Human Plasmatic Fibronectin Films as Proactive Coatings to Improve Implant Biointegration

2022 ◽  
Vol 9 ◽  
Author(s):  
Anamar Miranda ◽  
Damien Seyer ◽  
Carla Palomino-Durand ◽  
Houda Morakchi-Goudjil ◽  
Mathilde Massonie ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Cell Attachment ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Extracellular Matrix Protein ◽  
Matrix Remodeling ◽  
Layer By Layer ◽  
Anionic Polymer ◽  
Material Contact ◽  
Enhance Cell Attachment

The success of stable and long-term implant integration implies the promotion, control, and respect of the cell microenvironment at the site of implantation. The key is to enhance the implant–host tissue cross talk by developing interfacial strategies that guarantee an optimal and stable seal of soft tissue onto the implant, while preventing potential early and late infection. Indeed, implant rejection is often jeopardized by lack of stable tissue surrounding the biomaterial combined with infections which reduce the lifespan and increase the failure rate of implants and morbidity and account for high medical costs. Thin films formed by the layer-by-layer (LbL) assembly of oppositely charged polyelectrolytes are particularly versatile and attractive for applications involving cell–material contact. With the combination of the extracellular matrix protein fibronectin (Fn, purified from human plasma) and poly-L-lysine (PLL, exhibiting specific chain lengths), we proposed proactive and biomimetic coatings able to guarantee enhanced cell attachment and exhibiting antimicrobial properties. Fn, able to create a biomimetic interface that could enhance cell attachment and promote extracellular cell matrix remodeling, is incorporated as the anionic polymer during film construction by the LbL technic whereas PLL is used as the cationic polymer for its capacity to confer remarkable antibacterial properties.

scholarly journals The Pathophysiological Significance of Fibulin-3

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1294
Author(s):  
Imogen Livingstone ◽  
Vladimir N. Uversky ◽  
Dominic Furniss ◽  
Akira Wiberg
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Structural Integrity ◽  
Association Studies ◽  
Retinal Dystrophy ◽  
Elastic Fibre ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Extracellular Matrix Protein ◽  
Genome Wide Association Studies ◽  
Research Fields

Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, EFEMP1 expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.

scholarly journals Thrombospondin 1 and Its Diverse Roles as a Regulator of Extracellular Matrix in Fibrotic Disease

2019 ◽  
Vol 67 (9) ◽  
pp. 683-699 ◽  
Author(s):  
Joanne E. Murphy-Ullrich
Keyword(s):  
Extracellular Matrix ◽  
Stress Responses ◽  
Transforming Growth Factor Beta ◽  
Renal Fibrosis ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Extracellular Matrix Protein ◽  
Matrix Remodeling ◽  
Matrix Assembly ◽  
Thrombospondin 1

Thrombospondin 1 (TSP1) is a matricellular extracellular matrix protein that has diverse roles in regulating cellular processes important for the pathogenesis of fibrotic diseases. We will present evidence for the importance of TSP1 control of latent transforming growth factor beta activation in renal fibrosis with an emphasis on diabetic nephropathy. Other functions of TSP1 that affect renal fibrosis, including regulation of inflammation and capillary density, will be addressed. Emerging roles for TSP1 N-terminal domain regulation of collagen matrix assembly, direct effects of TSP1–collagen binding, and intracellular functions of TSP1 in mediating endoplasmic reticulum stress responses in extracellular matrix remodeling and fibrosis, which could potentially affect renal fibrogenesis, will also be discussed. Finally, we will address possible strategies for targeting TSP1 functions to treat fibrotic renal disease.

scholarly journals Macrophages promote prosclerotic responses in cultured rat mesangial cells: a mechanism for the initiation of glomerulosclerosis.

1997 ◽  
Vol 8 (10) ◽  
pp. 1525-1536
Author(s):  
I Z Pawluczyk ◽  
K P Harris
Keyword(s):  
Growth Factor ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Platelet Derived Growth Factor ◽  
Minor Role ◽  
Dependent Manner ◽  
The Matrix

Glomerulosclerosis is the final outcome of a number of different causes of glomerular injury, during which the structures of the glomerulus are obliterated by extracellular matrix. Accumulating evidence suggests that infiltrating macrophages play a pivotal role in the progression to glomerulosclerosis. The present study defines the role played by macrophages at both cellular and molecular levels in the initiation of the sclerotic process in cultured rat mesangial cells. Macrophage-conditioned medium (MPCM) generated from thioglycollate-elicited, lipopolysaccharide-stimulated macrophages upregulated mesangial cell fibronectin production in a dose- and time-dependent manner, independently of cell proliferation. Immunoprecipitation of metabolically labeled 35S-fibronectin confirmed that the matrix protein was synthesized de novo. The genes for fibronectin and the matrix proteins laminin and collagen IV were also found to be upregulated 2.86 +/- 0.24-, 4.94 +/- 0.17-, and 3.03 +/- 0.31-fold over controls, respectively (P < 0.001). Macrophage modulation of matrix turnover was suggested by an upregulation of both transin and tissue inhibitor of metalloproteinase-1 gene transcription. Transforming growth factor (TGF) beta1, platelet-derived growth factor, tumor necrosis factor (TNF) alpha, or interleukin (IL)-1beta could not be detected in the MPCM per se; however, TGFbeta1 and platelet-derived growth factor AB were found to be secreted into mesangial cell culture supernatants. Secretion was augmented 1.69 +/- 0.16- and 2.28 +/- 0.28-fold, respectively (both P < 0.001), in response to MPCM. Northern blot analysis demonstrated that protein secretion had been preceded by upregulation of the genes for these cytokines (2.2 +/- 0.4-fold [P < 0.001] and 5.7 +/- 1.2-fold [P < 0.004], respectively). Incubation of MPCM with either neutralizing antibody or the growth factor receptor antagonist suramin demonstrated that TGFbeta1 played a significant, although minor, role in MPCM-stimulated fibronectin production. In conclusion, this study provides compelling evidence for a direct role of macrophages in the progression to glomerulosclerosis.

scholarly journals Serum Matrix Metalloproteinases and Left Atrial Remodeling—The Hoorn Study

2020 ◽  
Vol 21 (14) ◽  
pp. 4944
Author(s):  
Pauline B. C. Linssen ◽  
Hans-Peter Brunner-La Rocca ◽  
Casper G. Schalkwijk ◽  
Joline W. J. Beulens ◽  
Petra J. M. Elders ◽  
...  
Keyword(s):  
Left Atrial ◽  
Matrix Protein ◽  
Regression Coefficient ◽  
Population Based ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Volume Index ◽  
Extracellular Matrix Protein ◽  
Atrial Remodeling ◽  
Cvd Risk

Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study (n = 674), underwent echocardiography. Serum MMPs (i.e., MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI); 0.03 (0.01; 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI; −0.04 (−0.07; −0.01) and −0.04 (−0.06; −0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI; 0.04 (0.00; 0.07, p-interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI; −0.05 (−0.09; −0.01, p-interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex.

scholarly journals Abnormal expression of FAK and paxillin correlates with oral cancer invasion and metastasis

2021 ◽  
Author(s):  
Ming Song ◽  
Jiang Hu ◽  
Hai-Ying Quan
Keyword(s):  
Cancer Progression ◽  
Protein Interactions ◽  
Matrix Protein ◽  
Side Population ◽  
Extracellular Matrix Protein ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Downstream Target ◽  
Chemotherapy Drugs ◽  
The Matrix

Globally, the tenth most common cancer is the oral squamous cell carcinoma (OSCC) and the treatment strategy for improving of OSCC patients survival rate still remains a challenging one. Aberrant regulation of cell to extracellular matrix protein interactions leads to progression of human cancers. The focal adhesion kinase (FAK) and its downstream target paxillin have been implicated in cancer growth, migration, invasion and metastasis of different cancers. However, the clinical significance of FAK and paxillin in OSCC is not well characterized so far. In the present work, we showed that relative mRNA and protein expressions of FAK and paxillin are significantly higher in side population (SP) cells of OSCC cell line SCC-55. Concomitantly, the matrix metalloproteinase-11 (MMP-11) level is also significantly elevated in SP cells. The enhanced expression of paxillin is strongly correlated with increased chemoresistance, proliferation rate, migration and invasion potential of SP cells. In addition, inhibition of paxillin expression by RNAi makes SP cells more sensitive to chemotherapy drugs. Therefore, our results suggest that paxillin over expression might play a significant role in cancer progression, invasion and chemoresistance of OSCC.

Expression of fibulin-2 by fibroblasts and deposition with fibronectin into a fibrillar matrix

1996 ◽  
Vol 109 (12) ◽  
pp. 2895-2904 ◽  
Author(s):  
T. Sasaki ◽  
H. Wiedemann ◽  
M. Matzner ◽  
M.L. Chu ◽  
R. Timpl
Keyword(s):  
Matrix Protein ◽  
Human Fibroblasts ◽  
Extracellular Matrix Protein ◽  
In Vitro Assays ◽  
Collagen Vi ◽  
Immunogold Staining ◽  
The Matrix ◽  
Immunological Assays

The extracellular matrix protein fibulin-2 was shown to be a typical product of cultured human and mouse fibroblasts by several immunological assays. It is secreted and deposited in cells and tissues as a disulfide-bonded oligomer identical in size to the previously described recombinant fibulin-2. Most of the fibroblast fibulin-2 is deposited into a dense fibrillar meshwork which requires treatment with EDTA and/or 6 M urea for solubilization. Fibulin-2 and fibronectin are synthesized at equivalent levels and both colocalize in the fibrils as shown by immunofluorescence. Metabolic labelling and pulse-chase studies demonstrated fibulin-2 oligomers in detergent extracts of cells and their rapid translocation to extracellular EDTA-sensitive assembly forms. Unlike for fibronectin and fibulin-1 only a little fibulin-2 was found in the cell culture medium. Immunogold staining of confluent human fibroblasts showed localization of fibulin-2 to a fine meshwork or bundles of amorphous microfibrils in the matrix. This also demonstrated a distinct colocalization of fibulin-2 and fibronectin at the electron microscope level, indicating that the interaction between these two protein shown in in vitro assays may also exist in situ. No distinct colocalization of both proteins could, however, be observed with cross-striated fibrils of collagen I and collagen VI microfibrils.

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