Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration

Missinato, Maria A.; Saydmohammed, Manush; Zuppo, Daniel A.; Rao, Krithika S.; Opie, Graham W.; Kühn, Bernhard; Tsang, Michael

doi:10.1242/dev.157206

Cited by 61 publications

(82 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 Missinato et al reported that DUSP6 attenuated Ras/MAPK signalling during regeneration and that suppression of DUSP6 expression could enhance cardiac repair. 28 In our study, CSE exposure up-regulated DUSP6 in HBE cells and lung F I G U R E 5 Overexpression of DUSP6 reverses the inhibition of airway inflammation and fibrosis mediated by HBE cells and lung fibroblasts after TUG1 knockdown. A and B, Expression of DUSP6 was determined in CSE-treated HBE cells and lung fibroblasts transfected with shTUG1 or DUSP6 alone or co-transfected with shTUG1 and DUSP6.…”

Section: Discussionmentioning

confidence: 47%

Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD

Yuan

Wang

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is primarily caused by cigarette smoke (CS)‐induced chronic inflammation. In this study, we investigated the function and mechanism of action of the long non‐coding RNA (lncRNA) taurine‐up‐regulated gene 1 (TUG1) in CS‐induced COPD. We found that the expression of TUG1 was significantly higher in the sputum cells and lung tissues of patients with COPD as compared to that in non‐smokers, and negatively correlated with the percentage of predicted forced expiratory volume in 1 second. In addition, up‐regulation of TUG1 was observed in CS‐exposed mice, and knockdown of TUG1 attenuated inflammation and airway remodelling in a mouse model. Moreover, TUG1 expression was higher in CS extract (CSE)‐treated human bronchial epithelial cells and lung fibroblasts, whereas inhibition of TUG1 reversed CSE‐induced inflammation and collagen deposition in vitro. Mechanistically, TUG1 promoted the expression of dual‐specificity phosphatase 6 (DUSP6) by sponging miR‐145‐5p. DUSP6 overexpression reversed TUG1 knockdown‐mediated inhibition of inflammation and airway remodelling. These findings suggested an important role of TUG1 in the pathological alterations associated with CS‐mediated airway remodelling in COPD. Thus, TUG1 may be a promising therapeutic target in CS‐induced airway inflammation and fibroblast activation.

show abstract

Section: Discussionmentioning

confidence: 47%

Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD

Yuan

Wang

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…DUSP6-/-mice with larger hearts was not due to hypertrophy, but rather to hypercellularity of the myocytes. A recent study confirmed a similar finding in the zebrafish heart by suppressing the Dusp6 function, which showed that DUSP6 attenuated Ras/MAPK signaling during regeneration, and inactivation of DUSP6 could enhance cardiac repair [52]. Opposite to the activation of ERK1/2, multiple lines of DUSP6 contained in the mouse heart were specifically generated [48].…”

Section: Targeting Phosphatases and Mapk Scaffold Proteinssupporting

confidence: 53%

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

Yan

Zeng

et al. 2021

Cardiol J.

View full text Add to dashboard Cite

Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2(ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPKKs, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.

show abstract

“…The preference for AFOG staining may likely be explained by a higher sensitivity for Collagen in particular in zebrafish as suggested by Poss et al [9]. Eight out of the 45 studies [9,29,36,66,73,89,90,94] evaluated the extent of heart regeneration by quantifying the amount of fibrosis on heart tissue sections in 2D where the area of collagen was compared to the total area of the ventricle.…”

Section: Qualitative and Quantitative Analysis Of Cardiac Outgrowthmentioning

confidence: 99%

“…In our systematical analysis we identified a total number of six studies [7,12,49,[87][88][89] that used a functional heart test as a measurement for cardiac recovery after AR. Three of these studies [7,49,89] used electrocardiography (ECG) while the other half [12,87,88] performed echocardiography.…”

Section: Analysis Of Heart Functionmentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Exposition of Methods used for Quantification of Heart Regeneration after Apex Resection in Zebrafish

Belling

Hofmeister

Andersen

2020

Cells

View full text Add to dashboard Cite

Myocardial infarction (MI) is a worldwide condition that affects millions of people. This is mainly caused by the adult human heart lacking the ability to regenerate upon injury, whereas zebrafish have the capacity through cardiomyocyte proliferation to fully regenerate the heart following injury such as apex resection (AR). But a systematic overview of the methods used to evidence heart regrowth and regeneration in the zebrafish is lacking. Herein, we conducted a systematical search in Embase and Pubmed for studies on heart regeneration in the zebrafish following injury and identified 47 AR studies meeting the inclusion criteria. Overall, three different methods were used to assess heart regeneration in zebrafish AR hearts. 45 out of 47 studies performed qualitative (37) and quantitative (8) histology, whereas immunohistochemistry for various cell cycle markers combined with cardiomyocyte specific proteins was used in 34 out of 47 studies to determine cardiomyocyte proliferation qualitatively (6 studies) or quantitatively (28 studies). For both methods, analysis was based on selected heart sections and not the whole heart, which may bias interpretations. Likewise, interstudy comparison of reported cardiomyocyte proliferation indexes seems complicated by distinct study designs and reporting manners. Finally, six studies performed functional analysis to determine heart function, a hallmark of human heart injury after MI. In conclusion, our data implies that future studies should consider more quantitative methods eventually taking the 3D of the zebrafish heart into consideration when evidencing myocardial regrowth after AR. Furthermore, standardized guidelines for reporting cardiomyocyte proliferation and sham surgery details may be considered to enable inter study comparisons and robustly determine the effect of given genes on the process of heart regeneration.Cells 2020, 9, 548 2 of 16 the compensatory mechanism after ischemia or injury, are assumed to favor fibrotic healing and hypertrophy instead of regeneration and cardiomyocyte proliferation [2,5]. Unfortunately, fibrotic healing may result in loss of heart contractility, leading to various complications and symptoms such as arrhythmias that also contribute to an increase in morbidity and mortality [5]. Today, only heart transplantation and palliative medication is offered as treatment of MI. Thus, a substantial effort is ongoing worldwide to develop regenerative therapies that can reduce mortality and improve life quality for millions of people [6].

show abstract

Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration

Cited by 61 publications

References 64 publications

Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD

Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

A Systematic Exposition of Methods used for Quantification of Heart Regeneration after Apex Resection in Zebrafish

Contact Info

Product

Resources

About