Potential role of MG53 in the regulation of transforming-growth-factor-β1-induced atrial fibrosis and vulnerability to atrial fibrillation

2018 ◽  
Vol 362 (2) ◽  
pp. 436-443 ◽  
Author(s):  
Jingwen Guo ◽  
Fengpeng Jia ◽  
Yingjiu Jiang ◽  
Qiang Li ◽  
Yucheng Yang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Potential Role ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Atrial Fibrosis

scholarly journals The fate of the primary cilium during myofibroblast transition

2014 ◽  
Vol 25 (5) ◽  
pp. 643-657 ◽  
Author(s):  
Matthew Rozycki ◽  
Monika Lodyga ◽  
Jessica Lam ◽  
Maria Zena Miranda ◽  
Károly Fátyol ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sonic Hedgehog ◽  
Primary Cilium ◽  
Potential Role ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Related Transcription Factor ◽  
Necessary And Sufficient ◽  
Organ Fibrosis

Myofibroblasts, the culprit of organ fibrosis, can originate from mesenchymal and epithelial precursors through fibroblast–myofibroblast and epithelial–myofibroblast transition (EMyT). Because certain ciliopathies are associated with fibrogenesis, we sought to explore the fate and potential role of the primary cilium during myofibroblast formation. Here we show that myofibroblast transition from either precursor results in the loss of the primary cilium. During EMyT, initial cilium growth is followed by complete deciliation. Both EMyT and cilium loss require two-hit conditions: disassembly/absence of intercellular contacts and transforming growth factor-β1 (TGFβ) exposure. Loss of E-cadherin–dependent junctions induces cilium elongation, whereas both stimuli are needed for deciliation. Accordingly, in a scratch-wounded epithelium, TGFβ provokes cilium loss exclusively along the wound edge. Increased contractility, a key myofibroblast feature, is necessary and sufficient for deciliation, since constitutively active RhoA, Rac1, or myosin triggers, and down-regulation of myosin or myocardin-related transcription factor prevents, this process. Sustained myosin phosphorylation and consequent deciliation are mediated by a Smad3-, Rac1-, and reactive oxygen species–dependent process. Transitioned myofibroblasts exhibit impaired responsiveness to platelet-derived growth factor-AA and sonic hedgehog, two cilium-associated stimuli. Although the cilium is lost during EMyT, its initial presence contributes to the transition. Thus myofibroblasts represent a unique cilium-less entity with profoundly reprogrammed cilium-related signaling.

scholarly journals Myocardial fibrosis and atrial fibrillation

2018 ◽  
pp. 71-76 ◽  
Author(s):  
S. V. Grigoryan ◽  
L. G. Azarapetyan ◽  
K. G. Adamyan
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Matrix Metalloproteases ◽  
Diagnostic Methods ◽  
Atrial Fibrosis ◽  
Non Invasive ◽  
Level Measurement

Atrial fibrillation is the most prevalent arrhythmia, and tends to progress. Any structural changes in the heart may lead to its progressive remodelling with increased deposition of connective tissue and fibrosis. Predominance of collagen types I and III synthesis over its degradation leads to accumulation of fibers and to fibrosis. Increase of atrial fibrosis is usually found on autopsy and biopsy. There is relation revealed, of atrial fibrosis grade and postsurgery atrial fibrillation. The mechanisms participating in the structural remodelling and progression of atrial fibrosis are not studied well enough, but there is known role of renin-angiotensinaldosterone system, transforming growth factor, inflammation and matrix metalloproteases. As an alternative, one should consider non-invasive diagnostic methods: magnetic resonance imaging of the heart and biomarkers level measurement. Hyperactivation of the renin-angiotensin-aldosterone system facilitates structural remodelling of the heart and progression of atrial fibrosis. Hyperexpression of the transforming growth factor leads to selective atrial fibrosis, heterogeneity of excitation conduction and fibrillation onset. Matrix metalloproteases are the marker of extracellular degradation. Study of fibrosis biomarkers makes it to increase significantly the efficacy of atrial fibrillation course prediction.

scholarly journals MG53/CAV1 regulates transforming growth factor-β1 signaling-induced atrial fibrosis in atrial fibrillation

Cell Cycle ◽  
2020 ◽  
Vol 19 (20) ◽  
pp. 2734-2744
Author(s):  
Meixia Zhang ◽  
Hechuan Wang ◽  
Xiaowen Wang ◽  
Mengjun Bie ◽  
Kai Lu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Atrial Fibrosis

scholarly journals The Exploration of Poor Ovarian Response–Related Risk Factors: A Potential Role of Growth Differentiation Factor 8 in Predicting Ovarian Response in IVF-ET Patient

2021 ◽  
Vol 12 ◽  
Author(s):  
Long Bai ◽  
Huihui Pan ◽  
Yinjun Zhao ◽  
Qingqing Chen ◽  
Yu Xiang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Growth Factor ◽  
Potential Role ◽  
Transforming Growth Factor ◽  
Ovarian Response ◽  
Poor Ovarian Response ◽  
Aberrant Expression ◽  
Differentiation Factor ◽  
Ivf Et

Controlled ovarian hyperstimulation (COH) is the most common therapeutic protocol to obtain a considerable number of oocytes in IVF-ET cycles. To date, the risk factors affecting COH outcomes remain elusive. Growth differentiation factor 8 (GDF-8), a member of transforming growth factor β (TGF-β) superfamily, has been long discerned as a crucial growth factor in folliculogenesis, and the aberrant expression of GDF-8 is closely correlated with the reproductive diseases. However, less is known about the level of GDF-8 in IVF-ET patients with different ovarian response. In the present study, the potential risk factors correlated with ovarian response were explored using logistic regression analysis methods. Meanwhile, the expression changes of GDF-8 and its responsible cellular receptors in various ovarian response patients were determined. Our results showed that several factors were intensely related to poor ovarian response (POR), including aging, obesity, endometriosis, surgery history, and IVF treatment, while irregular menstrual cycles and PCOS contribute to hyperovarian response (HOR). Furthermore, POR patients exhibited a decrease in numbers of MII oocytes and available embryos, thereby manifesting a lower clinical pregnancy rate. The levels of GDF-8, ALK5, and ACVR2B in POR patients were higher compared with those in control groups, whereas the expression level of ACVR2A decreased in poor ovarian response patients. In addition, clinical correlation analysis results showed that the concentration of GDF-8 was negatively correlated with LH and estradiol concentration and antral follicle count. Collectively, our observations provide a novel insight of ovarian response–associated risk factors, highlighting the potential role of GDF-8 levels in ovarian response during COH process.

scholarly journals A Review of the Molecular Mechanisms Underlying Cardiac Fibrosis and Atrial Fibrillation

2021 ◽  
Vol 10 (19) ◽  
pp. 4430
Author(s):  
Grażyna Sygitowicz ◽  
Agata Maciejak-Jastrzębska ◽  
Dariusz Sitkiewicz
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Signalling Pathways ◽  
Ang Ii ◽  
Atrial Fibrosis ◽  
Genes Encoding ◽  
Tgf Β1

The cellular and molecular mechanism involved in the pathogenesis of atrial fibrosis are highly complex. We have reviewed the literature that covers the effectors, signal transduction and physiopathogenesis concerning extracellular matrix (ECM) dysregulation and atrial fibrosis in atrial fibrillation (AF). At the molecular level: angiotensin II, transforming growth factor-β1, inflammation, and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodelling in AF. We conclude that the Ang-II-MAPK and TGF-β1-Smad signalling pathways play a major, central role in regulating atrial fibrotic remodelling in AF. The above signalling pathways induce the expression of genes encoding profibrotic molecules (MMP, CTGF, TGF-β1). An important mechanism is also the generation of reactive oxygen species. This pathway induced by the interaction of Ang II with the AT2R receptor and the activation of NADPH oxidase. Additionally, the interplay between cardiac MMPs and their endogenous tissue inhibitors of MMPs, is thought to be critical in atrial ECM metabolism and fibrosis. We also review recent evidence about the role of changes in the miRNAs expression in AF pathophysiology and their potential as therapeutic targets. Furthermore, keeping the balance between miRNA molecules exerting anti-/profibrotic effects is of key importance for the control of atrial fibrosis in AF.

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