PMID- 36193063 OWN - NLM STAT- MEDLINE DCOM- 20221005 LR - 20240118 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Tumor Necrosis Factor-Alpha Disrupts Cx43-Mediated Corneal Endothelial Gap Junction Intercellular Communication. PG - 4824699 LID - 10.1155/2022/4824699 [doi] LID - 4824699 AB - Connexin43 (Cx43)-mediated gap junctions are vital in maintaining corneal endothelium homeostasis. Tumor necrosis factor-alpha (TNF-alpha) is among the most important inflammatory factors which cause corneal endothelial dysfunction in various eye diseases. However, the effect of TNF-alpha on Cx43-mediated gap junctions of the corneal endothelium remains undefined. In the current research, we determined the effect of TNF-alpha on gap junction intercellular communication (GJIC) in rabbit corneal endothelium. To evaluate alterations of GJIC, if any, we treated ex vivo cultured rabbit corneal endothelium with different concentrations of TNF-alpha (2-20 ng/ml). The localization of Cx43 was analyzed by immunostaining, while RT-qPCR and western blot were used to profile the expression of Cx43 and zonula occludens-1 (ZO-1). The association between ZO-1 and Cx43 was evaluated using immunoprecipitation and double staining. GJIC activity was determined by the scrap loading and dye transfer assay (SLDT). Our data demonstrated that a high concentration of TNF-alpha (10 ng/ml and 20 ng/ml) disrupts the Cx43 mediated gap junction distribution in rabbit corneal endothelium and suppresses the expression of Cx43 protein. Furthermore, rabbit corneal endothelial GJIC was inhibited due to the decreased association between the ZO-1 and Cx43 proteins. Current results demonstrate that TNF-alpha inhibits corneal endothelial GJIC via decreasing the association between ZO-1 and Cx43, disrupting the distribution of Cx43, and downregulating the expression of Cx43 protein. This study offers a new theoretical foundation for diagnosing and treating corneal endothelial cell decompensation induced by elevated TNF-alpha in various eye diseases. CI - Copyright (c) 2022 Jufeng Meng et al. FAU - Meng, Jufeng AU - Meng J AUID- ORCID: 0000-0002-3035-7225 AD - School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. FAU - Xu, Ke AU - Xu K AUID- ORCID: 0000-0002-4423-1703 AD - Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Control of Tropical Diseases, School of Tropical Medicine, Hainan Medical University, Haikou 571199, China. FAU - Qin, Yinyin AU - Qin Y AD - Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. FAU - Liu, Ya AU - Liu Y AD - Department of Ophthalmology, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. FAU - Xu, Lin AU - Xu L AD - Department of Ophthalmology, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. FAU - Qiao, Shigang AU - Qiao S AUID- ORCID: 0000-0003-0309-8405 AD - Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. FAU - An, Jianzhong AU - An J AD - Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. FAU - Liu, Jianjun AU - Liu J AD - Department of Ophthalmology, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. FAU - Zhang, Zhenhao AU - Zhang Z AUID- ORCID: 0000-0001-5659-6315 AD - Institute of Clinical Medicine Research, Suzhou Science & Technology Town Hospital, Suzhou 215153, China. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20220919 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Connexin 43) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM RIN - Oxid Med Cell Longev. 2024 Jan 9;2024:9871986. PMID: 38234513 MH - Animals MH - Cell Communication/physiology MH - Cells, Cultured MH - *Connexin 43 MH - Gap Junctions/metabolism MH - Rabbits MH - *Tumor Necrosis Factor-alpha/metabolism PMC - PMC9526630 COIS- The authors declare that they have no conflict of interest. EDAT- 2022/10/05 06:00 MHDA- 2022/10/06 06:00 PMCR- 2022/09/19 CRDT- 2022/10/04 01:54 PHST- 2022/07/10 00:00 [received] PHST- 2022/08/23 00:00 [revised] PHST- 2022/08/27 00:00 [accepted] PHST- 2022/10/04 01:54 [entrez] PHST- 2022/10/05 06:00 [pubmed] PHST- 2022/10/06 06:00 [medline] PHST- 2022/09/19 00:00 [pmc-release] AID - 10.1155/2022/4824699 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Sep 19;2022:4824699. doi: 10.1155/2022/4824699. eCollection 2022.