ArticleCell communication and signaling : CCS2023
Connexin-43 hemichannels orchestrate NOD-like receptor protein-3 (NLRP3) inflammasome activation and sterile inflammation in tubular injury.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 29 citations in OpenAlex.
- The cardio-renal-metabolic role of the nod-like receptor protein-3 and senescence-associated secretory phenotype in early sodium/glucose cotransporter-2 inhibitor therapy in people with diabetes who have had a myocardial infarction.Diabetic medicine : a journal of the British Diabetic Association · 2025Trial
- The Immune System as a Proarrhythmic Mediator: A Novel Paradigm for the Development of New Antiarrhythmic Therapy.The Canadian journal of cardiology · 2026Review
- Zearalenone Induces Gap Junction Damage in Ovine Ovarian Granulosa Cells by Upregulating GPR30 and Activating the Oxidative Stress-NLRP3 Inflammasome Axis.Biomolecules · 2026Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Targeting inflammation in cardiometabolic disease: Icosapent ethyl modulates monocyte-derived macrophages isolated from patients with cardiovascular disease with or without type 2 diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2026Article
- Kidney Transcriptomic and Proteomic Analyses Provide New Insight into the Pathogenesis of IgA Nephropathy in Mice.Biochemical genetics · 2026Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Connexin-hemichannels-mediated ATP release causes lung injury following chlorine inhalation.American journal of physiology. Cell physiology · 2025Article
- Article
- Connexin43 hemichannel blockade turns microglia neuroprotective and mitigates cognitive deficits in a mouse model of amyloidosis.Nature communications · 2025Article
- Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.PLoS neglected tropical diseases · 2025Article
- Inflammasome Signaling in Cardiac Arrhythmias: Linking Inflammation, Fibrosis, and Electrical Remodeling.International journal of molecular sciences · 2025Review
- Repression of Connexin26 hemichannel activity protects the barrier function of respiratory airway epithelial cells against LPS-induced alteration.Cell communication and signaling : CCS · 2025Article
- Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2025Review
- Effect of heat stress on ileal epithelial barrier integrity in broilers divergently selected for high- and low-water efficiency.Frontiers in physiology · 2025Article
- Molecular mechanisms and therapeutic advances of peritubular capillary neogenesis in acute kidney injury.Frontiers in molecular biosciences · 2025Review
- Coordination of innate immune responses by connexins.Frontiers in immunology · 2025Review
- Endothelial-specific deletion of connexin 43 improves renal function and structure after acute kidney injury.Molecular medicine (Cambridge, Mass.) · 2024Article
- Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway.Renal failure · 2024Article
- Tonabersat suppresses priming/activation of the NOD-like receptor protein-3 (NLRP3) inflammasome and decreases renal tubular epithelial-to-macrophage crosstalk in a model of diabetic kidney disease.Cell communication and signaling : CCS · 2024Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWithout a viable cure, chronic kidney disease is a global health concern. Inflammatory damage in and around the renal tubules dictates disease severity and is contributed to by multiple cell types. Activated in response to danger associated molecular patterns (DAMPs) including ATP, the NOD-like receptor protein-3 (NLRP3) inflammasome is integral to this inflammation. In vivo, we have previously observed that increased expression of Connexin 43 (Cx43) is linked to inflammation in chronic kidney disease (CKD) whilst in vitro studies in human proximal tubule cells highlight a role for aberrant Cx43 hemichannel mediated ATP release in tubule injury. A role for Cx43 hemichannels in priming and activation of the NLRP3 inflammasome in tubule epithelial cells remains to be determined.
methodsUsing the Nephroseq database, analysis of unpublished transcriptomic data, examined gene expression and correlation in human CKD. The unilateral ureteral obstruction (UUO) mouse model was combined with genetic (tubule-specific Cx43 knockout) and specific pharmacological blockade of Cx43 (Peptide5), to explore a role for Cx43-hemichannels in tubule damage. Human primary tubule epithelial cells were used as an in vitro model of CKD.
resultsIncreased Cx43 and NLRP3 expression correlates with declining glomerular filtration rate and increased proteinuria in biopsies isolated from patients with CKD. Connexin 43-tubule deletion prior to UUO protected against tubular injury, increased expression of proinflammatory molecules, and significantly reduced NLRP3 expression and downstream signalling mediators. Accompanied by a reduction in F4/80 macrophages and fibroblast specific protein (FSP1
conclusionAberrant Cx43-hemichannel activity in kidney tubule cells contributes to tubule inflammation via activation of the NLRP3 inflammasome and downstream paracrine mediated cell signalling. Use of hemichannel blockers in targeting Cx43-hemichannels is an attractive future therapeutic target to slow or prevent disease progression in CKD. Video Abstract.
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