ArticleCell communication and signaling : CCS2020
Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 59 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
- Inhibition of (interstitial) P2YPflugers Archiv : European journal of physiology · 2026Article
- Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury.Cell death & disease · 2026Article
- Inhibition of (interstitial) P2YResearch square · 2026Article
- Molecular mechanisms of acute inflammation: systemic responses and kidney-specific pathophysiology.Function (Oxford, England) · 2026Review
- Inhibition of (interstitial) P2YbioRxiv : the preprint server for biology · 2026Article
- Interplay Between the Mineralocorticoid System, Inflammation, Hypertension, and Kidney Disease.Kidney360 · 2025Review
- Thermosensitive hydrogel composite with si-Cx43 nanoparticles and anti-VEGF agent for synergistic treatment of diabetic retinopathy.Materials today. Bio · 2025Article
- EphrinB2 alleviates tubulointerstitial fibrosis in diabetic kidney disease.Journal of translational medicine · 2025Article
- Ubiquitin-specific protease 38 modulates atrial fibrillation susceptibility in chronic kidney disease via STRAP stabilization and activation of TGF-β/SMAD signaling.Molecular medicine (Cambridge, Mass.) · 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
- Role of Pannexin 1, P2X7, and CFTR in ATP Release and Autocrine Signaling by Principal Cells of the Epididymis.Function (Oxford, England) · 2025Article
- Review
- 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
- The role of intercellular communication in diabetic nephropathy.Frontiers in immunology · 2024Review
- Blockade of connexin43-containing hemichannel attenuates the LPS-induced inflammatory response in human dental pulp cells by inhibiting the extracellular flux of ATP and HMGB1.Frontiers in oral health · 2024Article
- SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular CaBiological research · 2023Article
- Connexin-43 hemichannels orchestrate NOD-like receptor protein-3 (NLRP3) inflammasome activation and sterile inflammation in tubular injury.Cell communication and signaling : CCS · 2023Article
- Connexin 43 Promotes Neurogenesis via Regulating Aquaporin-4 after Cerebral Ischemia.Neurotoxicity research · 2023Article
- Knockdown of the long non‑coding RNA MALAT1 ameliorates TNF‑α‑mediated endothelial cell pyroptosis via the miR‑30c‑5p/Cx43 axis.Molecular medicine reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTubulointerstitial fibrosis represents the key underlying pathology of Chronic Kidney Disease (CKD), yet treatment options remain limited. In this study, we investigated the role of connexin43 (Cx43) hemichannel-mediated adenosine triphosphate (ATP) release in purinergic-mediated disassembly of adherens and tight junction complexes in early tubular injury.
methodsHuman primary proximal tubule epithelial cells (hPTECs) and clonal tubular epithelial cells (HK2) were treated with Transforming Growth Factor Beta1 (TGF-β1) ± apyrase, or ATPγS for 48 h. For inhibitor studies, cells were co-incubated with Cx43 mimetic Peptide 5, or purinergic receptor antagonists Suramin, A438079 or A804598. Immunoblotting, single-cell force spectroscopy and trans-epithelial electrical resistance assessed protein expression, cell-cell adhesion and paracellular permeability. Carboxyfluorescein uptake and biosensing measured hemichannel activity and real-time ATP release, whilst a heterozygous Cx43
resultsImmunohistochemistry of biopsy material from patients with diabetic nephropathy confirmed increased expression of purinergic receptor P2X7. TGF-β1 increased Cx43 mediated hemichannel activity and ATP release in hPTECs and HK2 cells. The cytokine reduced maximum unbinding forces and reduced cell-cell adhesion, which translated to increased paracellular permeability. Changes were reversed when cells were co-incubated with either Peptide 5 or P2-purinoceptor inhibitors. Cx43
conclusionData suggest that Cx43 mediated ATP release represents an initial trigger in early tubular injury via its actions on the adherens and tight junction complex. Since Cx43 is highly expressed in nephropathy, it represents a novel target for intervention of tubulointerstitial fibrosis in CKD. Video Abstract In proximal tubular epithelial cells (PTECs), tight junction proteins, including zona occuludens-1 (ZO-1), contribute to epithelial integrity, whilst the adherens junction protein epithelial (E)-cadherin (ECAD) maintains cell-cell coupling, facilitating connexin 43 (Cx43) gap junction-mediated intercellular communication (GJIC) and the direct transfer of small molecules and ions between cells. In disease, such as diabetic nephropathy, the pro-fibrotic cytokine transforming growth factor beta1 (TGF-β1) binds to its receptor and recruits SMAD2/3 signalling ahead of changes in gene transcription and up-regulation of Cx43-mediated hemichannels (HC). Uncoupled hemichannels permit the release of adenosine triphosphate (ATP) in to the extracellular space (↑[ATP]
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.