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However, the mechanisms underlying the renal damage remain poorly understood. The present study sought to elucidate the role of GSK3\u03b2 in enhancing mitochondrial endoplasmic reticulum (ER) membrane tethering and calcium (Ca\u00b2\u207a) exchange in the context of TCE sensitization\u2010induced renal injury. Our results showed that GSK3\u03b2 was localized within renal tubular epithelial cells and interacted with the IP3R1 calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) channel complex at mitochondria\u2010associated membranes (MAMs). TCE sensitization upregulated GSK3\u03b2 activity and the expression of IP3R1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel complex and its interactions, increased Ca\u00b2\u207a transfer from ER to mitochondria, Ca\u00b2\u207a overload, and apoptosis. The pharmacological inhibition of GSK3\u03b2 disrupted the protein interaction between IP3R and the Ca\u00b2\u207a channel complex, leading to a decrease in Ca\u00b2\u207a exchange between the ER and mitochondria. This reduction resulted in a decrease in the mitochondrial Ca\u00b2\u207a concentration and an increase in the antiapoptotic ability of the cell. Coherent changes to renal function variables were also observed, demonstrating the functional relevance of the GSK3\u03b2 pathway. Our results suggest that TCE sensitization damages renal tubular epithelial cells by promoting GSK3\u03b2\u2010mediated crosstalk between the ER and mitochondria, identifying a key mechanism for TCE\u2010induced renal injury. The findings from this study offer novel insights into the mechanisms of renal damage associated with TCE sensitization and lay down a foundation for the development of targeted preventive and therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70754","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:51:49Z","timestamp":1772967109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancement of Mitochondria\u2010Associated Membranes via GSK3\u03b2 Activation: A Key Contributor to Trichloroethylene\u2010Induced Renal Damage"],"prefix":"10.1002","volume":"40","author":[{"given":"Yu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qirui","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenghuan","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"You","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Dermatology First Affiliated Hospital of Anhui Medical University Hefei Anhui China"},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhao","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biosciences and Medicine Faculty of Health and Medical Sciences, University of Surrey Guildford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qixing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology First Affiliated Hospital of Anhui Medical University Hefei Anhui China"},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-604X","authenticated-orcid":false,"given":"Jiaxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health, Anhui Medical University Hefei Anhui China"},{"name":"Department of Dermatology First Affiliated Hospital of Anhui Medical University Hefei Anhui China"},{"name":"Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education Hefei Anhui China"},{"name":"School of Biosciences and Medicine Faculty of Health and Medical Sciences, University of Surrey Guildford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10803548.2021.2022956"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-022724-120525"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.174029"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fjurol.2024.102795"},{"key":"e_1_2_10_6_1","first-page":"450","article-title":"[Staging of Occupational Medicamentosa\u2010Like Dermatitis Due to Trichloroethylene]","volume":"38","author":"Lin D. 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