scholarly journals Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor

Blood ◽  
1990 ◽  
Vol 75 (7) ◽  
pp. 1509-1517 ◽  
Author(s):  
E Dejana ◽  
MG Lampugnani ◽  
M Giorgi ◽  
M Gaboli ◽  
PC Marchisio
Keyword(s):  
Endothelial Cell ◽  
Matrix Protein ◽  
Matrix Proteins ◽  
Extracellular Matrix Component ◽  
Integrin Receptor ◽  
Complex Type ◽  
Matrix Component ◽  
Cytoskeletal Organization ◽  
Subendothelial Matrix ◽  
Alpha V Beta 3

Abstract We have previously shown that fibrinogen (fg) acts as a subendothelial matrix protein in promoting human endothelial cell (EC) adhesion and cytoskeletal organization. In this study we report that EC spreading on fg, at variance with other matrix proteins, requires endogenous matrix protein synthesis and secretion. ECs, upon seeding on fg, promptly released and organized a fibronectin (fn) matrix. Fg was more effective than vitronectin (vn) in promoting the deposition of this protein. ECs treated with monensin to block matrix protein secretion still adhered to fg but did not properly organize their cytoskeleton and adhesion structures. In contrast, monensin did not affect EC spreading either on vn or on fn. Using antibodies to the alpha and beta chains of fn (alpha 5 beta 1) and vn (alpha v beta 3) receptors, it was found that ECs adherent to fg show clustering and organization in adhesion structures of both type of receptors. A faint staining of adhesion structures with alpha 2 but not alpha 3 and alpha 6 antibodies was also observed. Antibodies either to vn or fn receptors were able to disrupt the EC monolayer and to induce EC retraction and detachment, thus indicating that both receptors are important in maintaining a sustained EC adhesion to fg. However, when ECs were treated with monensin only the vn receptor was organized in adhesion structures while the fn receptor was diffusely distributed. This suggests that clustering of the fn receptor is mediated by the release of endogenous matrix proteins induced by the exposure to fg. In conclusion, fg has a peculiar and complex type of interaction with ECs since it requires endogenous matrix protein release and the recruitment of more than one adhesive receptor. This suggests a specific way of response of ECs to each extracellular matrix component.

scholarly journals Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor

Blood ◽  
1990 ◽  
Vol 75 (7) ◽  
pp. 1509-1517 ◽  
Author(s):  
E Dejana ◽  
MG Lampugnani ◽  
M Giorgi ◽  
M Gaboli ◽  
PC Marchisio
Keyword(s):  
Endothelial Cell ◽  
Matrix Protein ◽  
Matrix Proteins ◽  
Extracellular Matrix Component ◽  
Integrin Receptor ◽  
Complex Type ◽  
Matrix Component ◽  
Cytoskeletal Organization ◽  
Subendothelial Matrix ◽  
Alpha V Beta 3

We have previously shown that fibrinogen (fg) acts as a subendothelial matrix protein in promoting human endothelial cell (EC) adhesion and cytoskeletal organization. In this study we report that EC spreading on fg, at variance with other matrix proteins, requires endogenous matrix protein synthesis and secretion. ECs, upon seeding on fg, promptly released and organized a fibronectin (fn) matrix. Fg was more effective than vitronectin (vn) in promoting the deposition of this protein. ECs treated with monensin to block matrix protein secretion still adhered to fg but did not properly organize their cytoskeleton and adhesion structures. In contrast, monensin did not affect EC spreading either on vn or on fn. Using antibodies to the alpha and beta chains of fn (alpha 5 beta 1) and vn (alpha v beta 3) receptors, it was found that ECs adherent to fg show clustering and organization in adhesion structures of both type of receptors. A faint staining of adhesion structures with alpha 2 but not alpha 3 and alpha 6 antibodies was also observed. Antibodies either to vn or fn receptors were able to disrupt the EC monolayer and to induce EC retraction and detachment, thus indicating that both receptors are important in maintaining a sustained EC adhesion to fg. However, when ECs were treated with monensin only the vn receptor was organized in adhesion structures while the fn receptor was diffusely distributed. This suggests that clustering of the fn receptor is mediated by the release of endogenous matrix proteins induced by the exposure to fg. In conclusion, fg has a peculiar and complex type of interaction with ECs since it requires endogenous matrix protein release and the recruitment of more than one adhesive receptor. This suggests a specific way of response of ECs to each extracellular matrix component.

scholarly journals Signaling Mechanisms in the Regulation of Renal Matrix Metabolism in Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Meenalakshmi M. Mariappan
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Matrix Protein ◽  
Structural Changes ◽  
Mammalian Target Of Rapamycin ◽  
Adverse Outcomes ◽  
Matrix Proteins ◽  
Extracellular Matrix Protein ◽  
Renal Hypertrophy ◽  
Matrix Metabolism

Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-)regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes.

scholarly journals Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via induction of the extracellular matrix component hyaluronan

2017 ◽  
Vol 141 (4) ◽  
pp. 791-804 ◽  
Author(s):  
Sören Twarock ◽  
Christina Reichert ◽  
Ulrike Peters ◽  
Daniel J. Gorski ◽  
Katharina Röck ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Insulin Signalling ◽  
Tumour Progression ◽  
Extracellular Matrix Component ◽  
Matrix Component

scholarly journals miR-29b supplementation decreases expression of matrix proteins and improves alveolarization in mice exposed to maternal inflammation and neonatal hyperoxia

2017 ◽  
Vol 313 (2) ◽  
pp. L339-L349 ◽  
Author(s):  
Shaheen Durrani-Kolarik ◽  
Caylie A. Pool ◽  
Ashley Gray ◽  
Kathryn M. Heyob ◽  
Mary J. Cismowski ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Therapeutic Strategy ◽  
Matrix Protein ◽  
Matrix Proteins ◽  
Mouse Lung ◽  
Protein Levels ◽  
Matrix Deposition ◽  
Neonatal Hyperoxia ◽  
Prematurely Born Infants ◽  
Restrictive Lung Function

Even with advances in the care of preterm infants, chronic lung disease or bronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication. Among those diagnosed with BPD, a subset of infants develop severe BPD with disproportionate pulmonary morbidities. In addition to decreased alveolarization, these infants develop obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. Analyses of plasma obtained from preterm infants during the first week of life indicate that circulating miR-29b is suppressed in infants that subsequently develop BPD and that decreased circulating miR-29b is inversely correlated with BPD severity. Our mouse model mimics the pathophysiology observed in infants with severe BPD, and we have previously reported decreased pulmonary miR-29b expression in this model. The current studies tested the hypothesis that adeno-associated 9 (AAV9)-mediated restoration of miR-29b in the developing lung will improve lung alveolarization and minimize the deleterious changes in matrix deposition. Pregnant C3H/HeN mice received an intraperitoneal LPS injection on embryonic day 16 and newborn pups were exposed to 85% oxygen from birth to 14 days of life. On postnatal day 3, AAV9-miR-29b or AAV9-control was administered intranasally. Mouse lung tissues were then analyzed for changes in miR-29 expression, alveolarization, and matrix protein levels and localization. Although only modest improvements in alveolarization were detected in the AAV9-miR29b-treated mice at postnatal day 28, treatment completely attenuated defects in matrix protein expression and localization. Our data suggest that miR-29b restoration may be one component of a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.

Integrin receptor-mediated mobilisation of intranuclear calcium in rat osteoclasts

1993 ◽  
Vol 105 (1) ◽  
pp. 61-68 ◽  
Author(s):  
G. Shankar ◽  
I. Davison ◽  
M.H. Helfrich ◽  
W.T. Mason ◽  
M.A. Horton
Keyword(s):  
Cell Function ◽  
Bone Cells ◽  
Dynamic Equilibrium ◽  
Bone Matrix ◽  
Ion Concentration ◽  
Calcium Signal ◽  
Free Calcium ◽  
Integrin Receptor ◽  
Vitronectin Receptor ◽  
Alpha V Beta 3

Cell-matrix interactions have been shown to play an important role in regulating cell function and behaviour. In bone, where calcified matrix formation and resorption events are required to be in dynamic equilibrium, regulation of adhesive interactions between bone cells and their matrix is critical. The present study focuses on the osteoclast, the bone resorbing cell, as well as integrins, which are cell surface adhesion receptors that mediate osteoclast attachment to bone matrix. In osteoclasts, the most abundant integrin receptor is the vitronectin receptor (VNR, alpha v beta 3). The objective of the study was to investigate changes in intracellular calcium, a regulator of osteoclast function, following addition of peptides that bind integrins, in particular the alpha v beta 3 form of the vitronectin receptor (VNR), which is highly expressed in osteoclasts. The study demonstrated a unique spatial localisation of the calcium signal in response to cell membrane receptor occupancy by integrin ligands in rat osteoclasts. Addition of peptides with the Arg-Gly-Asp (RGD) sequence such as BSP-IIA, GRGDSP and GRGDS to rat osteoclasts evoked an immediate increase in free calcium ion concentration [Ca2+]i, localised to the nuclei and to the thin cytoplasmic skirt. These responses were inhibited by F11, a monoclonal antibody to the rat integrin beta 3 chain, as well as echistatin, a snake venom shown to colocalise with the alpha v chain in osteoclasts, suggesting that the calcium signal is mediated by the alpha v beta 3 form of VNR.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals NRF2 Activation Inhibits Both TGF-β1- and IL-13-Mediated Periostin Expression in Fibroblasts: Benefit of Cinnamaldehyde for Antifibrotic Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yasutaka Mitamura ◽  
Mika Murai ◽  
Chikage Mitoma ◽  
Masutaka Furue
Keyword(s):  
Dermal Fibroblasts ◽  
Treatment Modalities ◽  
Oxygen Species ◽  
Extracellular Matrix Component ◽  
Fibrotic Disease ◽  
Matrix Component ◽  
Nrf2 Activation ◽  
Life Threatening ◽  
Fibrotic Diseases ◽  
Tgf Β1

Systemic fibrosing or sclerotic disorders are life-threatening, but only very limited treatment modalities are available for them. In recent years, periostin (POSTN), a major extracellular matrix component, was established by several studies as a novel key player in the progression of systemic fibrotic disease. In this research, we revealed the involvement of oxidative stress in the expression of POSTN induced by TGF-β1 and IL-13 in dermal fibroblasts. We found that the antioxidant cinnamaldehyde activated the NRF2/HMOX1 pathway. Cinnamaldehyde also alleviated TGF-β1- and IL-13-mediated production of reactive oxygen species and subsequent POSTN upregulation in dermal fibroblasts. In contrast, NRF2 silencing abolished the cinnamaldehyde-mediated downregulation of POSTN. These results suggest that cinnamaldehyde is a broad inhibitor of POSTN expression covering both TGF-β1 and IL-13 signaling. Cinnamaldehyde may thus be beneficial for the treatment of systemic fibrotic diseases.

scholarly journals Autophagy Inhibitors Do Not Restore Peroxisomal Functions in Cells With the Most Common Peroxisome Biogenesis Defect

2021 ◽  
Vol 9 ◽  
Author(s):  
Femke C. C. Klouwer ◽  
Kim D. Falkenberg ◽  
Rob Ofman ◽  
Janet Koster ◽  
Démi van Gent ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Protein Import ◽  
Therapeutic Option ◽  
Cell Types ◽  
Matrix Proteins ◽  
Peroxisome Biogenesis ◽  
Metabolic Functions ◽  
Minimal Improvement ◽  
Different Cell Types ◽  
Autophagy Inhibition

Peroxisome biogenesis disorders within the Zellweger spectrum (PBD-ZSDs) are most frequently associated with the c.2528G>A (p.G843D) mutation in the PEX1 gene (PEX1-G843D), which results in impaired import of peroxisomal matrix proteins and, consequently, defective peroxisomal functions. A recent study suggested that treatment with autophagy inhibitors, in particular hydroxychloroquine, would be a potential therapeutic option for PBD-ZSD patients carrying the PEX1-G843D mutation. Here, we studied whether autophagy inhibition by chloroquine, hydroxychloroquine and 3-methyladenine indeed can improve peroxisomal functions in four different cell types with the PEX1-G843D mutation, including primary patient cells. Furthermore, we studied whether autophagy inhibition may be the mechanism underlying the previously reported improvement of peroxisomal functions by L-arginine in PEX1-G843D cells. In contrast to L-arginine, we observed no improvement but a worsening of peroxisomal metabolic functions and peroxisomal matrix protein import by the autophagy inhibitors, while genetic knock-down of ATG5 and NBR1 in primary patient cells resulted in only a minimal improvement. Our results do not support the use of autophagy inhibitors as potential treatment for PBD-ZSD patients, whereas L-arginine remains a therapeutically promising compound.

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