ArticleThe Journal of biological chemistry2011
Transcriptional suppression of connexin43 by TBX18 undermines cell-cell electrical coupling in postnatal cardiomyocytes.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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
48 citing papers in PubMed, 68 citations in OpenAlex.
- AAV-mediated long-term TBX18 expression causes cardiac fibrosis and fails to induce pacemaker activity in rodents.The Journal of clinical investigation · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Exosomal MicroRNA-1 Regulate Cx43 Expression via Tbx18 in Culture Atrial Fibroblasts under Rapid Electrical Stimulation.Acta Cardiologica Sinica · 2026Article
- Tissue elasticity modulates cardiac pacemaker cell automaticity.American journal of physiology. Heart and circulatory physiology · 2025Article
- Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications.Signal transduction and targeted therapy · 2024Review
- Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.Nature biomedical engineering · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies.Muscles (Basel, Switzerland) · 2023Review
- Harnessing cell reprogramming for cardiac biological pacing.Journal of biomedical science · 2023Review
- MicroRNA-dependent suppression of biological pacemaker activity induced by TBX18.Cell reports. Medicine · 2022Article
- Tbx18 Orchestrates Cytostructural Transdifferentiation of Cardiomyocytes to Pacemaker Cells by Recruiting the Epithelial-Mesenchymal Transition Program.Journal of proteome research · 2022Article
- Recombinant Adeno-Associated Viral Vector-Mediated Gene Transfer ofInternational journal of molecular sciences · 2022Article
- DNA Tension Probes Show that Cardiomyocyte Maturation Is Sensitive to the Piconewton Traction Forces Transmitted by Integrins.ACS nano · 2022Article
- Implementing Biological Pacemakers: Design Criteria for Successful.Circulation. Arrhythmia and electrophysiology · 2021Review
- Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study.PLoS computational biology · 2021Article
- Transcriptional and Epigenetic Landscape of Cardiac Pacemaker Cells: Insights Into Cellular Specialization in the Sinoatrial Node.Frontiers in physiology · 2021Review
- Cellular Reprogramming Approaches to Engineer Cardiac Pacemakers.Current cardiology reports · 2020Review
- Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells.Stem cells (Dayton, Ohio) · 2020Article
- The Quantitative Relationship among the Number of the Pacing Cells Required, the Dimension, and the Diffusion Coefficient.BioMed research international · 2020Article
- Engineered Cardiac Pacemaker Nodes Created by TBX18 Gene Transfer Overcome Source-Sink Mismatch.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-box transcription factors figure prominently in embryonic cardiac cell lineage specifications. Mesenchymal precursor cells expressing Tbx18 give rise to the heart's pacemaker, the sinoatrial node (SAN). We sought to identify targets of TBX18 transcriptional regulation in the heart by forced adenoviral overexpression in postnatal cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) transduced with GFP showed sarcolemmal, punctate Cx43 expression. In contrast, TBX18-transduced NRCMs exhibited sparse Cx43 expression. Both the transcript and protein levels of Cx43 were greatly down-regulated within 2 days of TBX18 transduction. Direct injection of TBX18 in the guinea pig heart in vivo inhibited Cx43 expression. The repressor activity of TBX18 on Cx43 was highly specific; protein levels of Cx45 and Cx40, which comprise the main gap junctions in the SAN and conduction system, were unchanged by TBX18. A reporter-based promoter assay demonstrated that TBX18 directly represses the Cx43 promoter. Phenotypically, TBX18-NRCMs exhibited slowed intercellular calcein dye transfer kinetics (421 ± 54 versus control 127 ± 43 ms). Intracellular Ca(2+) oscillations in control NRCM monolayers were highly synchronized. In contrast, TBX18 overexpression led to asynchronous Ca(2+) oscillations, demonstrating reduced cell-cell coupling. Decreased coupling led to slow electrical propagation; conduction velocity in TBX18 NRCMs slowed by more than 50% relative to control (2.9 ± 0.5 versus 14.3 ± 0.9 cm/s). Taken together, TBX18 specifically and directly represses Cx43 transcript and protein levels. Cx43 suppression leads to significant electrical uncoupling, but the preservation of other gap junction proteins supports slow action potential propagation, recapitulating a key phenotypic hallmark of the SAN.
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.