ArticleCell death & disease2019
Inhibition of gap junction composed of Cx43 prevents against acute kidney injury following liver transplantation.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Connexin 43-dependent mesenchymal stem cell mitochondrial transfer activates PGC1α disrupting oxidative-inflammation axis in ischemia-reperfusion injury.Signal transduction and targeted therapy · 2026Article
- The Role of Ubiquitination and Deubiquitination in the Pathogenesis of Acute Kidney Injury: Progress in Research.Biomedicines · 2025Review
- Mesenchymal Stem Cells Prevent SLC39A14-Dependent Hepatocyte Ferroptosis through Exosomal miR-16-5p in Liver Graft.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nephroprotective effects of substances of medicine food homology and traditional Chinese medicine phytochemicals against acute kidney injury.Frontiers in pharmacology · 2025Review
- CHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy.Communications biology · 2024Article
- Hepsin as a potential therapeutic target for alleviating acetaminophen-induced hepatotoxicity via gap-junction regulation and oxidative stress modulation.Cell biology and toxicology · 2024Article
- Role of connexin 43 in a rat model of periodontitis-induced renal injury.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2024Article
- Dose-dependent multi-organ injury following lipopolysaccharide gas inhalation.The Journal of international medical research · 2024Article
- Article
- Parthenolide Attenuates Sepsis-Induced Acute Kidney Injury in Rats by Reducing Inflammation.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Aldehyde Dehydrogenase 2 Protects the Kidney from Ischemia-Reperfusion Injury by Suppressing the IOxidative medicine and cellular longevity · 2023Article
- 18-α-glycyrrhetinic acid alleviates oxidative damage in periodontal tissue by modulating the interaction of Cx43 and JNK/NF-κB pathways.Frontiers in pharmacology · 2023Article
- Connexins in endothelial cells as a therapeutic target for solid organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Review
- The mechanisms through which auricular vagus nerve stimulation protects against cerebral ischemia/reperfusion injury.Neural regeneration research · 2022Article
- Melatonin Alleviates Acute Kidney Injury by Inhibiting NRF2/Slc7a11 Axis-Mediated Ferroptosis.Oxidative medicine and cellular longevity · 2022Article
- Verbena Attenuates Adriamycin-Induced Renal Tubular Injury via Inhibition of ROS-ERK1/2-NLRP3 Signal Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies.Expert reviews in molecular medicine · 2021Review
- Connexin32 activates necroptosis through Src-mediated inhibition of caspase 8 in hepatocellular carcinoma.Cancer science · 2021Article
- The mutual interplay of redox signaling and connexins.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Intercellular transmission of endoplasmic reticulum stress through gap junction targeted by microRNAs as a key step of diabetic kidney diseases?Annals of translational medicine · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Postoperative acute kidney injury (AKI) is a severe complication after liver transplantation (LT). Its deterioration and magnification lead to the increase in mortality. Connexin43 (Cx43) mediates direct transmission of intracellular signals between neighboring cells, always considered to be the potent biological basis of organ damage deterioration and magnification. Thus, we explored the effects of Cx43 on AKI following LT and its related possible mechanism. In this study, alternations of Cx43 expression were observed in 82 patients, receiving the first-time orthotopic LT. We built autologous orthotopic liver transplantation (AOLT) models with Sprague-Dawley (SD) rats in vivo, and hypoxia-reoxygenation (H/R) or lipopolysaccharide (LPS) pretreatment models with kidney tubular epithelial cells (NRK-52E) in vitro, both of which were the most important independent risk factors of AKI following LT. Then, different methods were used to alter the function of Cx43 channels to determine its protective effects on AKI. The results indicated that patients with AKI suffering from longer time of tracheal intubation or intensive care unit stay, importantly, had significantly lower survival rate at postoperative 30 days and 3 years. In rat AOLT models, as Cx43 was inhibited with heptanol, postoperative AKI was attenuated significantly. In vitro experiments, downregulation of Cx43 with selective inhibitors, or siRNA protected against post-hypoxic NRK-52E cell injuries caused by H/R and/or LPS, while upregulation of Cx43 exacerbated the above-mentioned cell injuries. Of note, alternation of Cx43 function regulated the content of reactive oxygen species (ROS), which not only mediated oxidative stress and inflammation reactions effectively, but also regulated necroptosis. Therefore, we concluded that Cx43 inhibition protected against AKI following LT through attenuating ROS transmission between the neighboring cells. ROS alternation depressed oxidative stress and inflammation reaction, which ultimately reduced necroptosis. This might offer new insights for targeted intervention for organ protection in LT, or even in other major surgeries.
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