articles+ search results
2 articles+ results
Analysis of Variance, Animals, Basic Helix-Loop-Helix Transcription Factors genetics, E-Box Elements physiology, Extracellular Matrix genetics, Extracellular Matrix metabolism, Genetic Vectors, Humans, Male, Mice, Mice, Knockout, NIH 3T3 Cells, Promoter Regions, Genetic, Rats, Rats, Sprague-Dawley, Transcriptional Activation, Transfection, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, Basic Helix-Loop-Helix Transcription Factors metabolism, Gene Expression Regulation, Matrix Metalloproteinase 2 genetics, Myocardium cytology, and Myofibroblasts physiology
Remodeling of the cardiac extracellular matrix is responsible for a number of the detrimental effects on heart function that arise secondary to hypertension, diabetes and myocardial infarction. This remodeling consists both of an increase in new matrix protein synthesis, and an increase in the expression of matrix metalloproteinases (MMPs) that degrade existing matrix structures. Previous studies utilizing knockout mice have demonstrated clearly that MMP2 plays a pathogenic role during matrix remodeling, thus it is important to understand the mechanisms that regulate MMP2 gene expression. We have shown that the transcription factor scleraxis is an important inducer of extracellular matrix gene expression in the heart that may also control MMP2 expression. In the present study, we demonstrate that scleraxis directly transactivates the proximal MMP2 gene promoter, resulting in increased histone acetylation, and identify a specific E-box sequence in the promoter to which scleraxis binds. Cardiac myo-fibroblasts isolated from scleraxis knockout mice exhibited dramatically decreased MMP2 expression; however, scleraxis over-expression in knockout cells could rescue this loss. We further show that regulation of MMP2 gene expression by the pro-fibrotic cytokine TGFβ occurs via a scleraxis-dependent mechanism: TGFβ induces recruitment of scleraxis to the MMP2 promoter, and TGFβ was unable to up-regulate MMP2 expression in cells lacking scleraxis due to either gene knockdown or knockout. These results reveal that scleraxis can exert control over both extracellular matrix synthesis and breakdown, and thus may contribute to matrix remodeling in wound healing and disease.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Adult, Anxiety psychology, Case-Control Studies, Cohort Studies, Depression psychology, Electroencephalography, Epilepsy, Temporal Lobe psychology, Female, Humans, Male, Middle Aged, Risk Assessment, Seizures psychology, Epilepsy epidemiology, Seizures epidemiology, and Somatoform Disorders epidemiology
Objective: We sought to examine the clinical and electrographic differences between patients with combined epileptic (ES) and psychogenic nonepileptic seizures (PNES) and age- and gender-matched patients with ES-only and PNES-only.
Methods: Data from 138 patients (105 women [77%]), including 46 with PNES/ES (39±12years), 46 with PNES-only (39±11years), and 46 with ES-only (39±11years), were compared using logistic regression analysis after adjusting for clustering effect.
Results: In the cohort with PNES/ES, ES antedated PNES in 28 patients (70%) and occurred simultaneously in 11 (27.5%), while PNES were the initial presentation in only 1 case (2.5%); disease duration was undetermined in 6. Compared with those with ES-only, patients with PNES/ES had higher depression and anxiety scores, shorter-duration electrographic seizures, less ES absence/staring semiology (all p≤0.01), and more ES arising in the right hemisphere, both in isolation and in combination with contralateral brain regions (61% vs. 41%; p=0.024, adjusted for anxiety and depression) and tended to have less ES arising in the left temporal lobe (13% vs. 28%; p=0.054). Compared with those with PNES-only, patients with PNES/ES tended to show fewer right-hemibody PNES events (7% vs. 23%; p=0.054) and more myoclonic semiology (10% vs. 2%; p=0.073).
Conclusions: Right-hemispheric electrographic seizures may be more common among patients with ES who develop comorbid PNES, in agreement with prior neurobiological studies on functional neurological disorders.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Books, media, physical & digital resources