ArticleCellular signalling2013
p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation.
Article in Cellular signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.Cardiovascular research · 2018Pooled it
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- Exercise intensity-dependent cardiac telocyte expansion is associated with physiological growth despite JAK/STAT pathway inactivity in male Wistar rats.Experimental physiology · 2026Article
- Causal relevance of the JAK/STAT pathway for cardioprotection via cold acclimation.Scientific reports · 2026Article
- Harnessing glucocorticoid receptor antagonism to enhance the efficacy of cardiac regenerative growth factors and cytokines.Nature cardiovascular research · 2026Article
- Sleep recovery ameliorates submandibular salivary gland inflammation associated with paradoxical sleep deprivation in male Wistar rats.Journal of applied oral science : revista FOB · 2025Article
- IL-6 Does Not Influence the Expression ofInternational journal of molecular sciences · 2024Article
- Extramedullary hematopoiesis in cancer.Experimental & molecular medicine · 2024Review
- Muscone inhibits angiotensin II-induced cardiac hypertrophy through the STAT3, MAPK and TGF-β/SMAD signaling pathways.Molecular biology reports · 2023Article
- Cardiovascular manifestations of inflammatory bowel diseases and the underlying pathogenic mechanisms.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Review
- Pathophysiological Effects of Various Interleukins on Primary Cell Types in Common Heart Disease.International journal of molecular sciences · 2023Review
- Cardiac-specific ITCH overexpression ameliorates septic cardiomyopathyJournal of molecular and cellular cardiology plus · 2022Article
- Stimulation of Osteoclast Formation by Oncostatin M and the Role of WNT16 as a Negative Feedback Regulator.International journal of molecular sciences · 2022Review
- gp130 Cytokines Activate Novel Signaling Pathways and Alter Bone Dissemination in ER+ Breast Cancer Cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Leukemia Inhibitory Factor: An Important Cytokine in Pathologies and Cancer.Biomolecules · 2022Review
- Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function.Basic research in cardiology · 2021Review
- VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms.International journal of molecular sciences · 2021Article
- The emerging role of leukemia inhibitory factor in cancer and therapy.Pharmacology & therapeutics · 2021Review
- IL-6/STAT3 Is a Promising Therapeutic Target for Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Leukemia Inhibitory Factor Induces Proopiomelanocortin via CRH/CRHR Pathway in Mouse Trophoblast.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The effect of differential signalling by IL-6 and leukaemia inhibitory factor (LIF) which signal by gp130 homodimerisation or LIFRβ/gp130 heterodimerisation on survival and hypertrophy was studied in neonatal rat cardiomyocytes. Both LIF and IL-6 [in the absence of soluble IL-6 receptor (sIL-6Rα)] activated Erk1/2, JNK1/2, p38-MAPK and PI3K signalling peaking at 20min and induced cytoprotection against simulated ischemia-reperfusion injury which was blocked by the MEK1/2 inhibitor PD98059 but not the p38-MAPK inhibitor SB203580. In the absence of sIL-6R, IL-6 did not induce STAT1/3 phosphorylation, whereas IL-6/sIL-6R and LIF induced STAT1 and STAT3 phosphorylation. Furthermore, IL-6/sIL-6R induced phosphorylation of STAT1 Tyr(701) and STAT3 Tyr(705) were enhanced by SB203580. IL-6 and pheneylephrine (PE), but not LIF, induced cardiomyocyte iNOS expression and nitric oxide (NO) production. IL-6, LIF and PE induced cardiomyocyte hypertrophy, but with phenotypic differences in ANF and SERCA2 expression and myofilament organisation with IL-6 more resembling PE than LIF. Transfection of cardiomyocytes with full length or truncated chimaeric gp130 cytoplasmic domain/Erythropoietin receptor (EpoR) extracellular domain fusion constructs showed that the membrane proximal Box 1 and Box 2 containing region of gp130 was necessary and sufficient for MAPK and PI3K activation; hypertrophy; SERCA2 expression and iNOS/NO induction in the absence of JAK/STAT activation. In conclusion, IL-6 can signal in cardiomyocytes independent of sIL-6R and STAT1/3 and furthermore, that Erk1/2 and PI3K activation by IL-6 are both necessary and sufficient for induced cardioprotection. In addition, p38-MAPK may act as a negative feedback regulator of JAK/STAT activation in cardiomyocytes.
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Registered trials
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