Search results for "CTG"
showing 10 items of 22 documents
4-Dechloro-14-deoxy-oxacyclododecindione and 14-deoxy-oxacylododecindione, two inhibitors of inducible connective tissue growth factor expression fro…
2015
Connective tissue growth factor (CTGF/CCN2), a member of the CCN superfamily of secreted cysteine-rich glycoproteins, is a central mediator of tissue remodeling and fibrosis. CTGF is suggested to be an important down-stream effector of transforming growth factor-beta (TGF-β) signaling and has therefore reached considerable pathophysiological relevance because of its involvement in the pathogenesis of fibrotic diseases, atherosclerosis, skin scarring, and other conditions with excess production of connective tissue. In a search for inhibitors of inducible CTGF expression from fungi, two new macrocyclic lactones, namely 4-dechloro-14-deoxy-oxacyclododecindione (1) and 14-deoxy-oxacylododecind…
TGF-β Signaling Pathways in Different Compartments of the Lower Airways of Patients With Stable COPD
2017
Background: The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-β pathway protein expression in patients with stable COPD. Methods: The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis. Results: TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium…
Myocardial hypertrophy is associated with inflammation and activation of endocannabinoid system in patients with aortic valve stenosis.
2013
article i nfo Article history: Received 1 February 2013 Accepted 22 March 2013 Aims: Endocannabinoids and their receptors have been associated with cardiac adaptation to injury, inflam- mation and fibrosis. Experimental studies suggested a role for inflammatory reaction and active remodeling in myocardial hypertrophy, but they have not been shown in human hypertrophy. We investigated the asso- ciation of the endocannabinoid system with myocardial hypertrophy in patients with aortic stenosis. Main methods: Myocardial biopsies were collected from patients with aortic stenosis (AS) and atrial myxoma as controls during surgery. Histological and molecular analysis of endocannabinoids and their r…
Transcript profiling identifies novel key players mediating the growth inhibitory effect of NS-398 on human pancreatic cancer cells
2010
Pancreatic cancer is one of the most aggressive human malignancies with an increasing incidence worldwide. Despite an increase in the number of systemic treatments available for pancreatic cancer, the impact of therapy on the clinical course of the disease has been modest, underscoring an urgent need for new therapeutic options. Although selective cyclooxygenase-2 inhibitors have been demonstrated to have cancer-preventive effects, the mechanism of their effects is not clearly known. Moreover, there have been no unbiased studies to identify novel molecular targets of NS-398 regarding pancreatic cancer. Here we undertook a gene expression profiling study to identify novel molecular targets m…
FGF-9 overexpression prevents pleural fibrosis induced by intra-pleural adenovirus injection in mice
2015
Introduction: Lung fibrosis is associated with the reactivation of molecular pathways involved in lung development. Mesothelial cells are involved in the fibrotic lung process but their exact role is debated. Fibroblast Growth Factor-9 (FGF-9) is expressed by epithelial cells and visceral pleura during embryonic lung development. Mice homozygous for a targeted disruption of FGF-9 exhibit lung hypoplasia with reduced mesenchyme and early postnatal death. The aim of this study was to evaluate the role of FGF-9 expression by mesothelial cells in the adult lung. We used adenovirus-mediated (FGF-9) gene transfer in mesothelial cells in vivo. Material and Methods: AdFGF9 or a control adenovirus (…
Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo.
2009
Abstract Background and purpose HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro . Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo . Materials and methods Four hours to 24h after total body irradiation (6Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5Gy and analyses were performed 3weeks after the first radiation treatment. Molecular markers of inflammation and f…
Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy
2021
Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSALR mouse model and patient-d…
Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model
2015
ABSTRACT Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1) disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apopto…
Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3
2007
Tissue repair is a well-orchestrated biological process involving numerous soluble mediators, and an imbalance between these factors may result in impaired repair and fibrosis. Transforming growth factor (TGF)-beta is a key profibrotic element in this process and it is thought that its three isoforms act in a similar way. Here, we report that TGF-beta3 administered to rat lungs using transient overexpression initiates profibrotic effects similar to those elicited by TGF-beta1, but causes less severe and progressive changes. The data suggest that TGF-beta3 does not lead to inhibition of matrix degradation in the same way as TGF-beta1, resulting in non-fibrotic tissue repair. Further, TGF-bet…
miR-7 Restores Phenotypes in Myotonic Dystrophy Muscle Cells by Repressing Hyperactivated Autophagy
2019
International audience; Unstable CTG expansions in the 3' UTR of the DMPK gene are responsible for myotonic dystrophy type 1 (DM1) condition. Muscle dysfunction is one of the main contributors to DM1 mortality and morbidity. Pathways by which mutant DMPK trigger muscle defects, however, are not fully understood. We previously reported that miR-7 was downregulated in a DM1 Drosophila model and in biopsies from patients. Here, using DM1 and normal muscle cells, we investigated whether miR-7 contributes to the muscle phenotype by studying the consequences of replenishing or blocking miR-7, respectively. Restoration of miR-7 with agomiR-7 was sufficient to rescue DM1 myoblast fusion defects and…