ArticleMolecular endocrinology (Baltimore, Md.)2015
Role of sphingosine kinase/S1P axis in ECM remodeling of cardiac cells elicited by relaxin.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Sphingolipids: drivers of cardiac fibrosis and atrial fibrillation.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Relaxin in fibrotic ligament diseases: Its regulatory role and mechanism.Frontiers in cell and developmental biology · 2023Review
- Chronic treatment with serelaxin mitigates adverse remodeling in a murine model of ischemic heart failure and modulates bioactive sphingolipid signaling.Scientific reports · 2022Article
- Ceramide/protein phosphatase 2A axis is engaged in gap junction impairment elicited by PCB153 in liver stem-like progenitor cells.Molecular and cellular biochemistry · 2021Article
- An adiponectin-S1P autocrine axis protects skeletal muscle cells from palmitate-induced cell death.Lipids in health and disease · 2020Article
- S1P/S1P Receptor Signaling in Neuromuscolar Disorders.International journal of molecular sciences · 2019Review
- Sphingosine 1-Phosphate (S1P)/ S1P Receptor Signaling and Mechanotransduction: Implications for Intrinsic Tissue Repair/Regeneration.International journal of molecular sciences · 2019Review
- Heart Disease and Relaxin: New Actions for an Old Hormone.Trends in endocrinology and metabolism: TEM · 2018Review
- Relaxin activates AMPK-AKT signaling and increases glucose uptake by cultured cardiomyocytes.Endocrine · 2018Article
- Getting to the heart of the sphingolipid riddle.Current opinion in physiology · 2018Article
- The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis.Frontiers in pharmacology · 2018Review
- Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation.Stem cells international · 2018Article
- Structural commonality of C1q TNF-related proteins and their potential to activate relaxin/insulin-like family peptide receptor 1 signalling pathways in cancer cells.British journal of pharmacology · 2017Review
- Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?Frontiers in pharmacology · 2017Review
- Implication of sphingosin-1-phosphate in cardiovascular regulation.Frontiers in bioscience (Landmark edition) · 2016Review
- The Anti-fibrotic Actions of Relaxin Are Mediated Through a NO-sGC-cGMP-Dependent Pathway in Renal Myofibroblasts In Vitro and Enhanced by the NO Donor, Diethylamine NONOate.Frontiers in pharmacology · 2016Article
- Resuscitation of a dead cardiomyocyte.Heart failure reviews · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The initiation and progression of heart failure is linked to adverse cardiac remodeling of the extracellular matrix (ECM) during disease mainly through the deregulation of myocardial metalloproteinases (MMPs). Relaxin (RLX), a peptide hormone acting as a physiological cardiac effector, is a key regulator of ECM remodeling in reproductive and nonreproductive tissues. Studying primary cultures of mouse cardiac muscle cells and rat H9c2 cardiomyoblasts, we have obtained evidence for a new signaling pathway activated by RLX to induce ECM remodeling that involves the bioactive sphingolipids sphingosine-1-phosphate (S1P) and ceramide. In both cell populations, recombinant human RLX increased sphingosine kinase activity and S1P formation, whereas sphingomyelin and ceramide content were decreased in [(3)H]serine-labeled cells. According to the literature, RLX promoted MMP-2 and MMP-9 expression/release. Pharmacological inhibition of sphingolipid metabolism and silencing of sphingosine kinase 1, the enzyme responsible for S1P formation, were able to prevent MMP expression/release elicited by the hormone and induce the expression of tissue inhibitor of MMPs. In addition, we found that sphingolipid signaling is required for the regulation of connective tissue growth factor, a member of the CCN 1-3 family of genes that are involved in cell proliferation and differentiation. Finally, the induction of cardiomyoblast maturation induced by RLX was also found to be counteracted by inhibition of S1P formation. In conclusion, these findings provide a novel mechanism by which RLX acts on cardiac ECM remodeling and cardiac cell differentiation and offer interesting therapeutic options to prevent heart fibrosis and to favor myocardial regeneration.
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