{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:57:12Z","timestamp":1788544632055,"version":"build-2803163510"},"reference-count":41,"publisher":"SAGE Publications","issue":"1-3","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>This study investigated the regulatory effect of Mitofusin2 (Mfn2) on mitochondria-associated endoplasmic reticulum membrane (MAM) integrity and cellular injury in cisplatin-induced acute kidney injury (CP-AKI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      CP-AKI mice exhibited decreased expression of Mfn2, increased expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), abnormal mitochondrial morphology, and reduced MAMs integrity, accompanied by the activation of mitochondrial reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress (inositol-requiring enzyme 1 [IRE1] and PERK pathways). In\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      studies, CP-induced mitochondrial ROS, ER-stress activation, and increased apoptosis were accompanied by the downregulation of Mfn2 and MAMs integrity reduction in Boston University mouse proximal tubular cells (BUMPT) and human proximal tubular epithelial cells (HK-2). Pretreatment of BUMPT cells with the Mfn2 plasmid partially restored the integrity of MAMs, negatively controlled IRE1 and PERK pathways, and inhibited cell apoptosis. In contrast, ER-stress and MAMs integrity violations were increased after Mfn2 small-interfering RNA (siRNA) treatment in HK-2 cells under CP treatment. Coimmunoprecipitation analysis demonstrated that Mfn2 interacted with PERK and IRE1. Furthermore, the adenosine 5\u2032-monophosphate (AMP)-activated protein kinase (AMPK), acadesine (AICAR), had a similar effect to Mfn2 plasmid in the regulation of ER stress and MAMs. Conversely, the ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), had no effect on the expression of Mfn2 and MAMs integrity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      This is the first study to explore the association between MAMs, ER stress, and Mfn2 in CP-AKI. Downregulation of Mfn2 expression abolished the MAMs integrity, and induced ER stress, mitochondrial ROS, and tubular cell apoptosis. This suggests that the Mfn2-MAMs pathway is a potential therapeutic target in CP-AKI.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      40, 16\u201339.\n                    <\/jats:p>\n                    <jats:p>The Ethical Registration number of animal experiment in this study was CSU-2022-01-0095.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" orientation=\"portrait\" position=\"float\" xlink:href=\"10.1089_ars.2022.0178-img51001.jpg\"\/>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2022.0178","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T12:55:00Z","timestamp":1681390500000},"page":"16-39","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["Mitofusin2 Ameliorated Endoplasmic Reticulum Stress and Mitochondrial Reactive Oxygen Species Through Maintaining Mitochondria-Associated Endoplasmic Reticulum Membrane Integrity in Cisplatin-Induced Acute Kidney Injury"],"prefix":"10.1177","volume":"40","author":[{"given":"Yu-ting","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-bin","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhan","sequence":"additional","affiliation":[{"name":"International Medicine Department, Ningbo First Hospital, Zhejiang University, Ningbo, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3657-1529","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-mei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pneumology, The Third Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-0176","authenticated-orcid":false,"given":"Shikun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Third Xiangya Hospital, The Critical Kidney Disease Research Center, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.211847"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(11)61454-2"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.107"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.769213"},{"issue":"3","key":"e_1_3_5_6_1","first-page":"352","article-title":"Assessing cervical dislocation as a humane euthanasia method in mice","volume":"51","author":"Carbone L","year":"2012","unstructured":"Carbone L, , Carbone ET, , Yi EM, et al. 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