Search results for "TGF-β"
showing 10 items of 26 documents
Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization.
2020
ABSTRACTShprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This resul…
ceRNA Network Regulation of TGF-β, WNT, FOXO, Hedgehog Pathways in the Pharynx of Ciona robusta
2021
The transforming growth factor-β (TGF-β) family of cytokines performs a multifunctional signaling, which is integrated and coordinated in a signaling network that involves other pathways, such as Wintless, Forkhead box-O (FOXO) and Hedgehog and regulates pivotal functions related to cell fate in all tissues. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from immune system homeostasis to the quiescence and self-renewal of hematopoietic stem cells (HSCs). Recently an important role in post-transcription regulation has been attributed to two type of ncRNAs: microRNAs and pseudogenes. Ciona robusta, due to its philogenetic position close to verte…
TNFSF14 (LIGHT) Exhibits Inflammatory Activities in Lung Fibroblasts Complementary to IL-13 and TGF-β
2018
The cytokine TNFSF14 [homologous to Lymphotoxin, exhibits Inducible expression and competes with HSV Glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT)] has been shown in mouse models to be important for development of lung tissue remodeling that is characteristic of asthma, idiopathic pulmonary fibrosis (IPF), and systemic sclerosis (SSc). However, its cellular targets are not fully delineated. In the present report, we show that LTβR and HVEM, the receptors for LIGHT, are constitutively expressed in primary human lung fibroblasts (HLFs). We asked whether LIGHT could promote inflammatory and remodeling-relevant activity in HLFs and how this was similar to, or…
Is TGF-β1 a Biomarker of Huntington’s Disease Progression?
2021
Huntington’s disease (HD) is an autosomal dominant genetic disease that can be divided into preclinical and symptomatic stages. Due to the diverse HD phenotype, there is an urgent need to identify markers that would independently assess its severity. The aim of this study was to evaluate the use of plasma levels of TGF-β1 in the assessment of HD severity. One hundred HD patients and 40 healthy volunteers were included in the study. All HD patients underwent neurological and cognitive function assessment. TGF-β1 levels were determined in the plasma of all patients. The correlations between TGF-β1 levels and clinical profile and HD severity were also investigated. In symptomatic patients, cog…
β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD
2012
AbstractWe quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β2-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and T…
IL-10 and TGF-β1 gene polymorphisms in Greek patients with recurrent aphthous stomatitis.
2022
Recurrent aphthous stomatitis (RAS) is one of the most frequent inflammatory disorders of the oral mucosa. Cytokines, which play an important role in RAS pathogenesis, participate directly or indirectly in normal, immunological and inflammatory processes and are secreted from cells belonging to innate and adaptive immunity as a consequence of microbial and antigenic stimuli. Gene polymorphisms in specific cytokines may predispose to RAS development. The aim of this study was the investigation and association of IL-10 and TGF-β1 gene polymorphisms with RAS.Study's cohort consisted of 60 Greek patients diagnosed with RAS, including 40 patients with minor, 10 patients with major and 10 with he…
Bi-allelic LoF NRROS Variants Impairing Active TGF-β1 Delivery Cause a Severe Infantile-Onset Neurodegenerative Condition with Intracranial Calcifica…
2020
Negative regulator of reactive oxygen species (NRROS) is a leucine-rich repeat-containing protein that uniquely associates with latent transforming growth factor beta-1 (TGF- β1) and anchors it on the cell surface; this anchoring is required for activation of TGF-β1 in macrophages and microglia. We report six individuals from four families with bi-allelic variants in NRROS. All affected individuals had neurodegenerative disease with refractory epilepsy, developmental regression, and reduced white matter volume with delayed myelination. The clinical course in affected individuals began with normal development or mild developmental delay, and the onset of seizures occurred within the first ye…
Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy.
2016
Background Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Methods Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Results Treatment of mdx mice with ActRIIB-Fc resulted in significantly in…
SARS CoV2 infection _The longevity study perspectives
2021
Graphical abstract
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…