ArticleJournal of molecular cell biology2021
Induction of Wnt signaling antagonists and p21-activated kinase enhances cardiomyocyte proliferation during zebrafish heart regeneration.
Article in Journal of molecular cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Pooled it
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Mesenchymal-derived neural progenitors underlie localbioRxiv : the preprint server for biology · 2026Article
- Inhibiting L-type calcium channel promotes cardiomyocyte proliferation through activating the canonical Wnt signaling pathway.Acta pharmacologica Sinica · 2026Article
- Article
- Cardiac Regeneration in Adult Zebrafish: A Review of Signaling and Metabolic Coordination.Current cardiology reports · 2025Review
- The mechanism of secreted frizzled-related protein 1 in alleviating cardiomyocyte injury and heart failure.Frontiers in cardiovascular medicine · 2025Review
- Plasma SFRP2 hypermethylation as a diagnostic biomarker for dilated cardiomyopathy detected by methylation-specific PCR.American journal of translational research · 2025Article
- A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A small molecule compound 759 inhibits the wnt/beta-catenin signaling pathway via increasing the Axin protein stability.Medical oncology (Northwood, London, England) · 2024Article
- A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration.Cellular and molecular life sciences : CMLS · 2024Article
- Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration.Frontiers in cell and developmental biology · 2024Review
- leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Inflammation and DKK1-induced AKT activation contribute to endothelial dysfunction following NR2F2 loss.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Origin and function of activated fibroblast states during zebrafish heart regeneration.Nature genetics · 2022Article
- Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease.International journal of molecular medicine · 2022Article
- Control of cardiomyocyte differentiation timing by intercellular signaling pathways.Seminars in cell & developmental biology · 2021Review
- Phosphoproteomic Analysis Reveals Downstream PKA Effectors of AKAP Cypher/ZASP in the Pathogenesis of Dilated Cardiomyopathy.Frontiers in cardiovascular medicine · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Heart regeneration occurs by dedifferentiation and proliferation of pre-existing cardiomyocytes (CMs). However, the signaling mechanisms by which injury induces CM renewal remain incompletely understood. Here, we find that cardiac injury in zebrafish induces expression of the secreted Wnt inhibitors, including Dickkopf 1 (Dkk1), Dkk3, secreted Frizzled-related protein 1 (sFrp1), and sFrp2, in cardiac tissue adjacent to injury sites. Experimental blocking of Wnt activity via Dkk1 overexpression enhances CM proliferation and heart regeneration, whereas ectopic activation of Wnt8 signaling blunts injury-induced CM dedifferentiation and proliferation. Although Wnt signaling is dampened upon injury, the cytoplasmic β-catenin is unexpectedly increased at disarrayed CM sarcomeres in myocardial wound edges. Our analyses indicated that p21-activated kinase 2 (Pak2) is induced at regenerating CMs, where it phosphorylates cytoplasmic β-catenin at Ser 675 and increases its stability at disassembled sarcomeres. Myocardial-specific induction of the phospho-mimetic β-catenin (S675E) enhances CM dedifferentiation and sarcomere disassembly in response to injury. Conversely, inactivation of Pak2 kinase activity reduces the Ser 675-phosphorylated β-catenin (pS675-β-catenin) and attenuates CM sarcomere disorganization and dedifferentiation. Taken together, these findings demonstrate that coordination of Wnt signaling inhibition and Pak2/pS675-β-catenin signaling enhances zebrafish heart regeneration by supporting CM dedifferentiation and proliferation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.