ArticleThe Journal of biological chemistry2019
Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 33 citations in OpenAlex.
- Ellagic acid attenuates myocardial fibrosis by suppressing Bmi1-mediated inhibition of the p53/p21 pathway in cardiac fibroblasts.Molecular and cellular biochemistry · 2026Article
- Downregulation of MLL1 Promotes Intestinal Epithelial Barrier Repair Through Gata4/Bmp4 Activation to Ameliorate Crohn's Disease-Like Colitis in Mice.Cell proliferation · 2026Article
- Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Mitochondrial fusion and cristae reorganization facilitate acquisition of cardiomyocyte identity during reprogramming of murine fibroblasts.Cell reports · 2025Article
- Decoding the epigenetic and transcriptional basis of direct cardiac reprogramming.Stem cells (Dayton, Ohio) · 2025Review
- Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis.Journal of translational medicine · 2025Review
- Macrophages suppress cardiac reprogramming of fibroblasts in vivo via IFN-mediated intercellular self-stimulating circuit.Protein & cell · 2024Article
- FGF4 and ascorbic acid enhance the maturation of induced cardiomyocytes by activating JAK2-STAT3 signaling.Experimental & molecular medicine · 2024Article
- 14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.Cell reports · 2024Article
- Robust small molecule-aided cardiac reprogramming systems selective to cardiac fibroblasts.iScience · 2023Article
- Can we stop one heart from breaking: triumphs and challenges in cardiac reprogramming.Current opinion in genetics & development · 2023Review
- Direct Reprogramming of Resident Non-Myocyte Cells and Its Potential for In Vivo Cardiac Regeneration.Cells · 2023Review
- In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter.Journal of visualized experiments : JoVE · 2022Article
- MIP-1Contrast media & molecular imaging · 2022Article
- Review
- BMI1 in the heart: Novel functions beyond tumorigenesis.EBioMedicine · 2021Review
- Sall4 and Myocd Empower Direct Cardiac Reprogramming From Adult Cardiac Fibroblasts After Injury.Frontiers in cell and developmental biology · 2021Article
- Strategies and Challenges to Improve Cellular Programming-Based Approaches for Heart Regeneration Therapy.International journal of molecular sciences · 2020Review
- Enhanced Generation of Induced Cardiomyocytes Using a Small-Molecule Cocktail to Overcome Barriers to Cardiac Cellular Reprogramming.Journal of the American Heart Association · 2020Article
- Bmi1 inhibitor PTC-209 promotes Chemically-induced Direct Cardiac Reprogramming of cardiac fibroblasts into cardiomyocytes.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 3 countries.
Funding
Abstract
Reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a potentially promising strategy for regenerating a damaged heart. However, low fibroblast-cardiomyocyte conversion rates remain a major challenge in this reprogramming. To this end, here we conducted a chemical screen and identified four agents, insulin-like growth factor-1, Mll1 inhibitor MM589, transforming growth factor-β inhibitor A83-01, and Bmi1 inhibitor PTC-209, termed IMAP, which coordinately enhanced reprogramming efficiency. Using α-muscle heavy chain-GFP-tagged mouse embryo fibroblasts as a starting cell type, we observed that the IMAP treatment increases iCM formation 6-fold. IMAP stimulated higher cardiac troponin T and α-actinin expression and increased sarcomere formation, coinciding with up-regulated expression of many cardiac genes and down-regulated fibroblast gene expression. Furthermore, IMAP promoted higher spontaneous beating and calcium transient activities of iCMs derived from neonatal cardiac fibroblasts. Intriguingly, we also observed that the IMAP treatment repressed many genes involved in immune responses, particularly those in specific C-C chemokine signaling pathways. We therefore investigated the roles of C-C motif chemokine ligand 3 (CCL3), CCL6, and CCL17 in cardiac reprogramming and observed that they inhibited iCM formation, whereas inhibitors of C-C motif chemokine receptor 1 (CCR1), CCR4, and CCR5 had the opposite effect. These results indicated that the IMAP treatment directly suppresses specific C-C chemokine signaling pathways and thereby enhances cardiac reprogramming. In conclusion, a combination of four chemicals, named here IMAP, suppresses specific C-C chemokine signaling pathways and facilitates Mef2c/Gata4/Tbx5 (MGT)-induced cardiac reprogramming, providing a potential means for iCM formation in clinical applications.
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.