scholarly journals Morphological alterations and NO-synthase expression in the heart after continuous light exposure of rats

2007 ◽  
pp. S71-S76
Author(s):  
Ľ Paulis ◽  
R Važan ◽  
F Šimko ◽  
O Pecháňová ◽  
J Styk ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Collagen Type ◽  
Light Exposure ◽  
Continuous Light ◽  
Collagen Type I ◽  
No Synthase ◽  
Collagen I ◽  
Heart Weight ◽  
Type I ◽  
Cardiac Morphology

Although exposure to continuous light is associated with hypertension and modulates the outcome of ischemia-reperfusion injury, less attention has been paid to its effects on cardiac morphology. We investigated whether 4-week exposure of experimental rats to continuous 24 h/day light can modify cardiac morphology, with focus on heart weight, fibrosis and collagen I/III ratio in correlation with NO-synthase expression. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light. After 4 weeks of treatment the absolute and the relative heart weights were determined and myocardial fibrosis and collagen type I/III ratio were evaluated using picrosirius red staining. Endothelial and inducible NO-synthase expression was detected immunohistochemically. The exposure of rats to continuous light resulted in an increase of body weight with proportionally increased heart weight. Myocardial fibrosis remained unaffected but collagen I/III ratio increased. Neither endothelial nor inducible NO-synthase expression was altered in light-exposed rats. We conclude that the loss of structural homogeneity of the myocardium in favor of collagen type I might increase myocardial stiffness and contribute to functional alterations after continuous light exposure.

scholarly journals Effect of Captopril and Melatonin on Fibrotic Rebuilding of the Aorta in 24 Hour Light-Induced Hypertension

2013 ◽  
pp. S135-S141 ◽  
Author(s):  
K. REPOVÁ-BEDNÁROVÁ ◽  
S. AZIRIOVÁ ◽  
J. HRENÁK ◽  
K. KRAJČÍROVIČOVÁ ◽  
M. ADAMCOVÁ ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Light Exposure ◽  
Continuous Light ◽  
Collagen Type I ◽  
Collagen I ◽  
Aortic Tissue ◽  
Type I ◽  
Collagen Iii ◽  
Induced Hypertension ◽  
Aortic Media

Chronic continuous light exposure leads to melatonin deficiency along with complex neurohumoral activation resulting in hypertension development in rats. The aim of this study was to show, whether continuous light induces fibrotic rebuilding of the aorta and whether the treatment with melatonin or angiotensin converting enzyme inhibitor captopril can prevent these potential alterations. In a six-week experiment, 3-month-old Wistar rats were divided into 4 groups (ten per group): controls, rats exposed to continuous light, exposed to continuous light plus treated with captopril (100 mg/kg/24 h) and exposed to continuous light plus treated with melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and collagen type I and III in the media of thoracic aorta were measured. Continuous light induced hypertension and fibrotic rebuilding of the aorta in terms of enhancement of collagen I and III concentration in the aortic media. Both captopril and melatonin prevented SBP rise and reduced collagen III concentration in the aorta. However, only melatonin reduced collagen I and the sum of collagen I and III in the aortic tissue. We conclude that in continuous light-induced hypertension, administration of melatonin, along with SBP reduction, decreases collagen I and III concentration in the aorta. It is suggested that antifibrotic effect of melatonin may reduce the stiffness of the aorta and small arteries and beneficially influence the nature of the pulse wave and peripheral vascular resistance.

scholarly journals Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts

2020 ◽  
Vol 133 (23) ◽  
pp. jcs248278 ◽  
Author(s):  
Ana M. Diaz-Espinosa ◽  
Patrick A. Link ◽  
Delphine Sicard ◽  
Ignasi Jorba ◽  
Daniel J. Tschumperlin ◽  
...  
Keyword(s):  
Collagen Type ◽  
Cathepsin K ◽  
Collagen Type I ◽  
D1 Receptor ◽  
Collagen I ◽  
Lung Fibroblasts ◽  
Type I ◽  
Cultured Fibroblasts ◽  
Normal Wound Healing

ABSTRACTMatrix resorption is essential to the clearance of the extracellular matrix (ECM) after normal wound healing. A disruption in these processes constitutes a main component of fibrotic diseases, characterized by excess deposition and diminished clearance of fibrillar ECM proteins, such as collagen type I. The mechanisms and stimuli regulating ECM resorption in the lung remain poorly understood. Recently, agonism of dopamine receptor D1 (DRD1), which is predominantly expressed on fibroblasts in the lung, has been shown to accelerate tissue repair and clearance of ECM following bleomycin injury in mice. Therefore, we investigated whether DRD1 receptor signaling promotes the degradation of collagen type I by lung fibroblasts. For cultured fibroblasts, we found that DRD1 agonism enhances extracellular cleavage, internalization and lysosomal degradation of collagen I mediated by cathepsin K, which results in reduced stiffness of cell-derived matrices, as measured by atomic force microscopy. In vivo agonism of DRD1 similarly enhanced fibrillar collagen degradation by fibroblasts, as assessed by tissue labeling with a collagen-hybridizing peptide. Together, these results implicate DRD1 agonism in fibroblast-mediated collagen clearance, suggesting an important role for this mechanism in fibrosis resolution.This article has an associated First Person interview with the first author of the paper.

Changes in extracellular matrix composition regulate cyclooxygenase-2 expression in human mesangial cells

2011 ◽  
Vol 300 (4) ◽  
pp. C907-C918 ◽  
Author(s):  
Matilde Alique ◽  
Laura Calleros ◽  
Alicia Luengo ◽  
Mercedes Griera ◽  
Miguel Ángel Iñiguez ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Collagen Type ◽  
Mesangial Cells ◽  
Collagen Type I ◽  
Collagen I ◽  
Type I ◽  
Camp Response Element ◽  
Response Element ◽  
Human Mesangial Cells ◽  
Cox 2

Glomerular diseases are characterized by a sustained synthesis and accumulation of abnormal extracellular matrix proteins, such as collagen type I. The extracellular matrix transmits information to cells through interactions with membrane components, which directly activate many intracellular signaling events. Moreover, accumulating evidence suggests that eicosanoids derived from cyclooxygenase (COX)-2 participate in a number of pathological processes in immune-mediated renal diseases, and it is known that protein kinase B (AKT) may act through different transcription factors in the regulation of the COX-2 promoter. The present results show that progressive accumulation of collagen I in the extracellular medium induces a significant increase of COX-2 expression in human mesangial cells, resulting in an enhancement in PGE2 production. COX-2 overexpression is due to increased COX-2 mRNA levels. The study of the mechanism implicated in COX-2 upregulation by collagen I showed focal adhesion kinase (FAK) activation. Furthermore, we observed that the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by collagen I and collagen I-induced COX-2 overexpression was abolished by PI3K and AKT inhibitors. Additionally, we showed that the cAMP response element (CRE) transcription factor is implicated. Finally, we studied COX-2 expression in an animal model, NG-nitro-l-arginine methyl ester hypertensive rats. In renal tissue and vascular walls, COX-2 and collagen type I content were upregulated. In summary, our results provide evidence that collagen type I increases COX-2 expression via the FAK/PI3K/AKT/cAMP response element binding protein signaling pathway.

scholarly journals Protein kinase C δ regulates the release of collagen type I from vascular smooth muscle cells via regulation of Cdc42

2012 ◽  
Vol 23 (10) ◽  
pp. 1955-1963 ◽  
Author(s):  
Justin Lengfeld ◽  
Qiwei Wang ◽  
Andrew Zohlman ◽  
Susana Salvarezza ◽  
Stephanie Morgan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Arterial Wall ◽  
Collagen Type ◽  
Collagen Type I ◽  
Collagen I ◽  
Type I ◽  
Kinase C

Collagen type I is the most abundant component of extracellular matrix in the arterial wall. Mice knocked out for the protein kinase C δ gene (PKCδ KO) show a marked reduction of collagen I in the arterial wall. The lack of PKCδ diminished the ability of arterial smooth muscle cells (SMCs) to secrete collagen I without significantly altering the intracellular collagen content. Moreover, the unsecreted collagen I molecules accumulate in large perinuclear puncta. These perinuclear structures colocalize with the trans-Golgi network (TGN) marker TGN38 and to a lesser degree with cis-Golgi marker (GM130) but not with early endosomal marker (EEA1). Associated with diminished collagen I secretion, PKCδ KO SMCs exhibit a significant reduction in levels of cell division cycle 42 (Cdc42) protein and mRNA. Restoring PKCδ expression partially rescues Cdc42 expression and collagen I secretion in PKCδ KO SMCs. Inhibition of Cdc42 expression or activity with small interfering RNA or secramine A in PKCδ WT SMCs eliminates collagen I secretion. Conversely, restoring Cdc42 expression in PKCδ KO SMCs enables collagen I secretion. Taken together, our data demonstrate that PKCδ mediates collagen I secretion from SMCs, likely through a Cdc42-dependent mechanism.

scholarly journals Phylogenetic analyses of ray-finned fishes (Actinopterygii) using collagen type I protein sequences

2021 ◽  
Vol 8 (8) ◽  
pp. 201955
Author(s):  
Virginia L. Harvey ◽  
Joseph N. Keating ◽  
Michael Buckley
Keyword(s):  
Amino Acid ◽  
Molecular Clock ◽  
Collagen Type ◽  
Average Rate ◽  
Phylogenetic Analyses ◽  
Collagen Type I ◽  
Higher Order ◽  
Amino Acid Sequences ◽  
Collagen I ◽  
Type I

Ray-finned fishes (Actinopterygii) are the largest and most diverse group of vertebrates, comprising over half of all living vertebrate species. Phylogenetic relationships between ray-finned fishes have historically pivoted on the study of morphology, which has notoriously failed to resolve higher order relationships, such as within the percomorphs. More recently, comprehensive genomic analyses have provided further resolution of actinopterygian phylogeny, including higher order relationships. Such analyses are rightfully regarded as the ‘gold standard’ for phylogenetics. However, DNA retrieval requires modern or well-preserved tissue and is less likely to be preserved in archaeological or fossil specimens. By contrast, some proteins, such as collagen, are phylogenetically informative and can survive into deep time. Here, we test the utility of collagen type I amino acid sequences for phylogenetic estimation of ray-finned fishes. We estimate topology using Bayesian approaches and compare the congruence of our estimated trees with published genomic phylogenies. Furthermore, we apply a Bayesian molecular clock approach and compare estimated divergence dates with previously published genomic clock analyses. Our collagen-derived trees exhibit 77% of node positions as congruent with recent genomic-derived trees, with the majority of discrepancies occurring in higher order node positions, almost exclusively within the Percomorpha. Our molecular clock trees present divergence times that are fairly comparable with genomic-based phylogenetic analyses. We estimate the mean node age of Actinopteri at ∼293 million years (Ma), the base of Teleostei at ∼211 Ma and the radiation of percomorphs beginning at ∼141 Ma (∼350 Ma, ∼250–283 Ma and ∼120–133 Ma in genomic trees, respectively). Finally, we show that the average rate of collagen (I) sequence evolution is 0.9 amino acid substitutions for every million years of divergence, with the α 3 (I) sequence evolving the fastest, followed by the α 2 (I) chain. This is the quickest rate known for any vertebrate group. We demonstrate that phylogenetic analyses using collagen type I amino acid sequences generate tangible signals for actinopterygians that are highly congruent with recent genomic-level studies. However, there is limited congruence within percomorphs, perhaps due to clade-specific functional constraints acting upon collagen sequences. Our results provide important insights for future phylogenetic analyses incorporating extinct actinopterygian species via collagen (I) sequencing.

scholarly journals Angiotensin II Activates Collagen Type I Gene in the Renal Cortex and Aorta of Transgenic Mice through Interaction with Endothelin and TGF-β

2001 ◽  
Vol 12 (12) ◽  
pp. 2701-2710
Author(s):  
Fadi Fakhouri ◽  
Sandrine Placier ◽  
Raymond Ardaillou ◽  
Jean-Claude Dussaule ◽  
Christos Chatziantoniou
Keyword(s):  
Angiotensin Ii ◽  
Transgenic Mice ◽  
Collagen Type ◽  
Renal Cortex ◽  
Collagen Type I ◽  
Collagen I ◽  
Type I ◽  
Cortical Slices ◽  
I Gene

ABSTRACT. Hypertension is frequently associated with the development of renal vascular fibrosis. This pathophysiologic process is due to the abnormal formation of extracellular matrix proteins, mainly collagen type I. In previous studies, it has been observed that the pharmacologic blockade of angiotensin II (Ang II) or endothelin (ET) blunted the development of glomerulo- and nephroangiosclerosis in nitric oxide-deficient hypertensive animals by inhibiting collagen I gene activation. The purpose of this study was to investigate whether and how AngII interacts with ET to activate the collagen I gene and whether transforming growth factor-β (TGF-β) could be a player in this interaction. Experiments were performedin vivoon transgenic mice harboring the luciferase gene under the control of the collagen I-α2 chain promoter (procolα2[I]). Bolus intravenous administration of AngII or ET produced a rapid, dose-dependent activation of collagen I gene in aorta and renal cortical slices (threefold increase over control at 2 h,P< 0.01). The AngII-induced effect on procolα2(I) was completely inhibited by candesartan (AngII type 1 receptor antagonist) and substantially blunted by bosentan (dual ET receptor antagonist) (P< 0.01), whereas the ET-induced activation of collagen I gene was blocked only by bosentan. In subsequent experiments, TGF-β (also administered intravenously) produced a rapid increase of procolα2(I) in aorta and renal cortical slices (twofold increase over control at 1 h,P< 0.01) that was completely blocked by decorin (scavenger of the active form of TGF-β). In addition, decorin attenuated the activation of collagen I gene produced by AngII (P< 0.01). These data indicate that AngII can activate collagen I gene in aorta and renal cortexin vivoby a mechanism(s) requiring participation and/or cooperation of ET and TGF-β.

scholarly journals Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure

2004 ◽  
Vol 43 (11) ◽  
pp. 2028-2035 ◽  
Author(s):  
Begoña López ◽  
Ramón Querejeta ◽  
Arantxa González ◽  
Eloy Sánchez ◽  
Mariano Larman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Myocardial Fibrosis ◽  
Collagen Type ◽  
Collagen Type I ◽  
Loop Diuretics ◽  
Type I

scholarly journals Beneficial Effects of Mineralocorticoid Receptor Antagonism on Myocardial Fibrosis in an Experimental Model of the Myxomatous Degeneration of the Mitral Valve

2020 ◽  
Vol 21 (15) ◽  
pp. 5372
Author(s):  
Jaime Ibarrola ◽  
Mattie Garaikoetxea ◽  
Amaia Garcia-Peña ◽  
Lara Matilla ◽  
Eva Jover ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Myocardial Fibrosis ◽  
Mineralocorticoid Receptor ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I ◽  
Myxomatous Degeneration ◽  
Human Cardiac Fibroblasts

Mitral valve prolapse (MVP) patients develop myocardial fibrosis that is not solely explained by volume overload, but the pathophysiology has not been defined. Mineralocorticoid receptor antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis in other heart diseases. We examined the role of MRA in myocardial fibrosis associated with myxomatous degeneration of the mitral valve. Myocardial fibrosis has been analyzed in a mouse model of mitral valve myxomatous degeneration generated by pharmacological treatment with Nordexfenfluramine (NDF) in the presence of the MRA spironolactone. In vitro, adult human cardiac fibroblasts were treated with NDF and spironolactone. In an experimental mouse, MRA treatment reduced interstitial/perivascular fibrosis and collagen type I deposition. MRA administration blunted NDF-induced cardiac expression of vimentin and the profibrotic molecules galectin-3/cardiotrophin-1. In parallel, MRA blocked the increase in cardiac non-fibrillar proteins such as fibronectin, aggrecan, decorin, lumican and syndecan-4. The following effects are blocked by MRA: in vitro, in adult human cardiac fibroblasts, NDF-treatment-induced myofibroblast activation, collagen type I and proteoglycans secretion. Our findings demonstrate, for the first time, the contribution of the mineralocorticoid receptor (MR) to the development of myocardial fibrosis associated with mitral valve myxomatous degeneration. MRA could be a therapeutic approach to reduce myocardial fibrosis associated with MVP.

microRNA-122 down-regulation may play a role in severe myocardial fibrosis in human aortic stenosis through TGF-β1 up-regulation

2013 ◽  
Vol 126 (7) ◽  
pp. 497-506 ◽  
Author(s):  
Javier Beaumont ◽  
Begoña López ◽  
Nerea Hermida ◽  
Blanche Schroen ◽  
Gorka San José ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Myocardial Fibrosis ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Down Regulation ◽  
Enzymatic Systems ◽  
Tgf Β1 ◽  
Stimulation Of

We have found an association of miR-122 down-regulation with myocardial fibrosis in AS patients, probably through TGF-β1 up-regulation and stimulation of the enzymatic systems involved in extracellular collagen type I synthesis and deposition.

Sign in / Sign up

Export Citation Format

Share Document