ArticleESC heart failure2021
Crosstalk between the activated Slit2-Robo1 pathway and TGF-β1 signalling promotes cardiac fibrosis.
Article in ESC heart failure, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- SLIT2 and ANGPTL3 as putative mediators linking obesity to atrial fibrillation: A Mendelian randomization study.Medicine · 2026Article
- Deletion of Robo4 worsens neuroinflammation in a mouse model of Alzheimer's disease.Physiological reports · 2026Article
- Targeting C/EBPβ to Suppress Myocardial Fibrosis in Hypertensive Heart Disease: Role of the ACE2/Ang-(1-7) Pathway.Journal of cellular and molecular medicine · 2026Article
- Extracellular Vesicles in the Heart-Organ Axis: From Inter-Organ Communication to Precision Nanomedicine for Heart Diseases.International journal of nanomedicine · 2026Review
- Effects of Slit2 on hypertrophic scar formation: an in vitro study in fibroblasts.Scientific reports · 2025Article
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- Alternative mRNA splicing in anthracycline-induced cardiomyopathy - a COG-ALTE03N1 report.Cardio-oncology (London, England) · 2025Article
- Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy.Nature reviews. Cancer · 2025Review
- Slit1 Promotes Hypertrophic Scar Formation Through the TGF-β Signaling Pathway.Medicina (Kaunas, Lithuania) · 2024Article
- Factors predicting the recurrence of atrial fibrillation after catheter ablation: A review.Heliyon · 2024Review
- Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024Review
- Identification of Shared Signature Genes and Immune Microenvironment Subtypes for Heart Failure and Chronic Kidney Disease Based on Machine Learning.Journal of inflammation research · 2024Article
- Possible mechanisms of SARS-CoV-2-associated myocardial fibrosis: reflections in the post-pandemic era.Frontiers in microbiology · 2024Review
- Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.Cellular & molecular biology letters · 2023Article
- Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1-srGAP1 pathway in a rat model of germinal matrix hemorrhage.Journal of neuroinflammation · 2023Article
- Slit2/Robo1 signaling inhibits small-cell lung cancer by targeting β-catenin signaling in tumor cells and macrophages.Molecular oncology · 2023Article
- Genome-Wide Association Study IdentifiesJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- CCN2/CTGF promotes liver fibrosis through crosstalk with the Slit2/Robo signaling.Journal of cell communication and signaling · 2023Article
- KCa3.1 Promotes Proinflammatory Exosome Secretion by Activating AKT/Rab27a in Atrial Myocytes during Rapid Pacing.Cardiovascular therapeutics · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPrevious reports indicated that the Slit2-Robo signalling pathway is involved in embryonic heart development and fibrosis in other solid organs, but its function in adult cardiac fibrosis has not been investigated. Here, we investigate the role of the Slit2-Robo1 signalling pathway in cardiac fibrosis. METHODS AND
resultsThe right atrial tissue samples were obtained from patients with valvular heart disease complicated by atrial fibrillation during heart valve surgery and from healthy heart donors. The fibrotic animal model is created by performing transverse aortic constriction (TAC) surgery. The Robo1, Slit2, TGF-β1, and collagen I expression levels in human and animal samples were evaluated by immunohistochemistry and western blot analysis. Echocardiography measured the changes in heart size and cardiac functions of animals. Angiotensin II (Ang II), Slit2-siRNA, TGF-β1-siRNA, recombinant Slit2, and recombinant TGF-β1 were transfected to cardiac fibroblasts (CFs) respectively to observe their effects on collagen I expression level. The right atrial appendage of patients with valvular heart disease complicated by atrial fibrillation found significantly up-regulated Slit2, Robo1, TGF-β1, and collagen I expression levels. TAC surgery leads to heart enlargement, cardiac fibrosis, and up-regulation of Slit2, Robo1, TGF-β1, and collagen I expression levels in animal model. Robo1 antagonist R5 and TGF-β1 antagonist SB431542 suppressed cardiac fibrosis in TAC mice. Treatment with 100 nM Ang II in CFs caused significantly increased Slit2, Robo1, Smad2/3, TGF-β1, collagen I, PI3K, and Akt expression levels. Transfecting Slit2-siRNA and TGF-β1-siRNA, respectively, into rat CFs significantly down-regulated Smad2/3 and collagen I expression, inhibiting the effects of Ang II. Recombinant Slit2 activated the TGF-β1/Smad signalling pathway in CFs and up-regulated Periostin, Robo1, and collagen I expression.
conclusionsThe Slit2-Robo1 signalling pathway interfered with the TGF-β1/Smad pathway and promoted cardiac fibrosis. Blockade of Slit2-Robo1 might be a new treatment for cardiac fibrosis.
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