ArticleMolecular and cellular biochemistry2013
Hypoxia induces connexin 43 dysregulation by modulating matrix metalloproteinases via MAPK signaling.
Article in Molecular and cellular biochemistry, 2013. 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, 57 citations in OpenAlex.
- Connexin 43 in Pathophysiology of Cardiac Diseases: From Molecular Mechanisms to Therapeutic Strategies.Physiological research · 2025Review
- Disrupting the interaction between connexin 43 and calmodulin restores gap junction function and mitigates reperfusion arrhythmias.Scientific reports · 2025Article
- NETs drive myocardial fibrosis in hypertension via an NF-κB/ferroptosis axis.Frontiers in immunology · 2025Article
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
- Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Deletion but Not Inhibition of Extracellular PCSK9 Reduces Infarct Sizes Ex Vivo but Not In Vivo.International journal of molecular sciences · 2022Article
- Trastuzumab and Doxorubicin Sequential Administration Increases Oxidative Stress and Phosphorylation of Connexin 43 on Ser368.International journal of molecular sciences · 2022Article
- Inhibitory Effect of Lotusine on Solar UV-Induced Matrix Metalloproteinase-1 Expression.Plants (Basel, Switzerland) · 2022Article
- The Role of Connexin in Ophthalmic Neovascularization and the Interaction between Connexin and Proangiogenic Factors.Journal of ophthalmology · 2022Review
- Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine β-coronavirus-induced neuroinflammation.Virology · 2022Article
- Plasmalogens Regulate Retinal Connexin 43 Expression and Müller Glial Cells Gap Junction Intercellular Communication and Migration.Frontiers in cell and developmental biology · 2022Article
- Hypoxia‑induced internalization of connexin 26 and connexin 43 in pulmonary epithelial cells is involved in the occurrence of non‑small cell lung cancer via the P53/MDM2 signaling pathway.International journal of oncology · 2019Article
- Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR-1-dependent pathway.Journal of cellular and molecular medicine · 2019Article
- The Role of Connexin-43 in the Inflammatory Process: A New Potential Therapy to Influence Keratitis.Journal of ophthalmology · 2019Review
- Astrocyte Mechano-Activation by High-Rate Overpressure Involves Alterations in Structural and Junctional Proteins.Frontiers in neurology · 2019Article
- Developmental Programming: Gestational Exposure to Excess Testosterone Alters Expression of Ovarian Matrix Metalloproteases and Their Target Proteins.Reproductive sciences (Thousand Oaks, Calif.) · 2018Article
- Protein⁻Protein Interactions with Connexin 43: Regulation and Function.International journal of molecular sciences · 2018Review
- The stress kinase JNK regulates gap junction Cx43 gene expression and promotes atrial fibrillation in the aged heart.Journal of molecular and cellular cardiology · 2018Article
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Miconazole protects blood vessels from MMP9-dependent rupture and hemorrhage.Disease models & mechanisms · 2017Article
- Can heart function lost to disease be regenerated by therapeutic targeting of cardiac scar tissue?Seminars in cell & developmental biology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Connexin 43 (Cx43) is a major structural protein found in the gap junctions of the ventricular myocardium and a major determinant of its electrical properties. The effects of matrix metalloproteinases (MMPs), the mitogen-activated protein kinase (MAPK) signaling pathway, transcription factor NF-kB, and activator protein-1 (AP-1)/c-Jun on the regulation of Cx43 gene expression in H9c2 cardiomyocytes were assessed. The MAPK signaling pathway (MEK/ERK1/2 and PI3K) and transcription factors NF-kB and AP-1/c-Jun were inhibited, then Cx43 expression was assessed using Western blot analysis, and MMP-9 activity was assessed using gelatin zymography. Hypoxia decreased the Cx43 protein level by approximately 30-50 %. Doxycycline (10 μg/mL), an inhibitor of MMP, markedly attenuated the hypoxia-induced downregulation of Cx43 protein expression at 6 h. The hypoxia-induced decrease in Cx43 protein expression was significantly reversed by U0126 (10 μM), a MEK/ERK1/2 inhibitor, at 6 and 12 h; LY294002 (30 μM), a PI3K inhibitor, downregulated Cx43 expression. Hypoxia-induced MMP-9 activation was inhibited by treatment with LY294002, U0126, and, most especially, U0126. JSH-23 (30 μM), an NF-kB inhibitor, and SP600125 (10 μM), an AP-1/c-Jun inhibitor, attenuated the loss of Cx43. These results suggest that MAPK signaling and the activities NF-kB and MMPs play an important roles in the regulation of Cx43 expression.
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Registered trials
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