ArticleJournal of neuroinflammation2020
Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- The Dual Role of Connexins in Stroke, Neurotrauma, Neurodegenerative and Psychiatric Disorders: A Global Systematic Review.Molecules (Basel, Switzerland) · 2026Pooled it
- NeuroD1-based in situ neural regeneration for the treatment of radiation-induced brain injury.Neural regeneration research · 2026Article
- YAP1 Upregulates Cytoskeleton Regulator ARHGEF1 and Tissue Regeneration Factor NEDD9 in a Multiplex Proteomic Study.Neurology international · 2026Article
- Plasma YAP1 as a biomarker for the prediction of occurrence, progression, and outcomes of sepsis-associated liver injury: a prospective observational study.BMC gastroenterology · 2026Observational
- CD204 regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following intracerebral hemorrhage.Scientific reports · 2026Article
- UBL4A as a suppressor of intracerebral hemorrhage by binding to MAPK14 and promoting MAPK14 ubiquitination.Genes & genomics · 2026Article
- Manipulation therapy alleviates neuropathic painThe Korean journal of pain · 2026Article
- Red Blood Cell-Derived Exosomes Deliver Complement C5 to Exacerbate Neuroinflammation and Neuronal Injury after Intracerebral Hemorrhage.Inflammation · 2026Article
- Microglial Membranes Wrapped Ultrasmall Medium-Entropy Ru Single-Atom Nanozyme: Enhanced Catalysis for Accelerating Inflammation/Redox Microenvironment Regulation in Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The CaCell reports. Medicine · 2026Article
- Inhibition of connexin hemichannels protects retinal ganglion cells against ocular nerve injury.Cellular and molecular life sciences : CMLS · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Effects of GABAAR modulators CL218872 and MRK-016 on neural repair and synaptic plasticity in mice with Intracerebral hemorrhage.PloS one · 2026Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- The involvement of 5-HT was necessary for EA-mediated improvement of post-stroke depression.Translational psychiatry · 2025Article
- Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals.CNS neuroscience & therapeutics · 2025Review
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- The causal association between 91 inflammatory Circulating proteins and intracerebral hemorrhage: A bidirectional two-sample Mendelian randomization study.Neurosurgical review · 2025Article
- Reactive astrocyte-derived exosomes enhance intracranial lymphatic drainage in mice after intracranial hemorrhage.Fluids and barriers of the CNS · 2025Article
- OAB-14 Attenuated Glymphatic System Disorder, Neuroinflammation and Dyskinesia in Parkinson's Disease Model Mice Induced by Rotenone.Neurochemical research · 2025Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIn the central nervous system (CNS), connexin 43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Similar to Cx43 overexpression, abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies. However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear.
methodsHemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH models in vitro and in vivo. After ICH injury, the Cx43 mimetic peptide Gap19 was used for treatment. Ethidium bromide (EtBr) uptake assays were used to measure the opening of Cx43Hcs. Western blotting and immunofluorescence were used to measure protein expression. qRT-PCR and ELISA were used to determine the levels of cytokines. Coimmunoprecipitation (Co-IP) and the Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins.
resultsIn this study, Cx43 expression upregulation and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19 significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition, Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture. However, Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased Yes-associated protein (YAP) nuclear translocation. This subsequently upregulated SOCS1 and SOCS3 expression and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor, verteporfin (VP), reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury.
conclusionsThis study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs. Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 has anti-inflammatory and neuroprotective effects after ICH injury.
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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 Socratic graph.