{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:43:36Z","timestamp":1791193416849,"version":"4.1.0"},"reference-count":57,"publisher":"SAGE Publications","issue":"13","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"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":[[2016,11]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aim:<\/jats:italic>\n                    <\/jats:bold>\n                    Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mammalian target of rapamycin complex 2 (mTORC2) mediates podocyte injury in diabetes.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    High glucose (HG)-induced podocyte injury reflected by alterations in the slit diaphragm protein podocin and podocyte depletion\/apoptosis. This was paralleled by activation of the Rictor\/mTORC2\/Akt pathway. HG also increased the levels of Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using small interfering RNA (siRNA)-targeting Rictor\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    decreased HG-induced Nox1 and Nox4, NADPH oxidase activity, restored podocin levels, and reduced podocyte depletion\/apoptosis. Inhibition of mTORC2 had no effect on mammalian target of rapamycin complex 1 (mTORC1) activation, described by our group to be increased in diabetes, suggesting that the mTORC2 activation by HG could mediate podocyte injury independently of mTORC1. In isolated glomeruli of OVE26 mice, there was a similar activation of the Rictor\/mTORC2\/Akt signaling pathway with increase in Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using antisense oligonucleotides targeting Rictor restored podocin levels, reduced podocyte depletion\/apoptosis, and attenuated glomerular injury and albuminuria.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    Our data provide evidence for a novel function of mTORC2 in NADPH oxidase-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    mTORC2 and\/or NADPH oxidase inhibition may represent a therapeutic modality for diabetic kidney disease.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    25, 703\u2013719.\n                  <\/jats:p>","DOI":"10.1089\/ars.2015.6562","type":"journal-article","created":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T22:22:23Z","timestamp":1468016543000},"page":"703-719","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":60,"title":["mTORC2 Signaling Regulates Nox4-Induced Podocyte Depletion in Diabetes"],"prefix":"10.1177","volume":"25","author":[{"given":"St\u00e9phanie","family":"Eid","sequence":"first","affiliation":[{"name":"American University of Beirut","place":["Lebanon"]},{"name":"Sorbonne Paris Cite University","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan","family":"Boutary","sequence":"additional","affiliation":[{"name":"American University of Beirut","place":["Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawthar","family":"Braych","sequence":"additional","affiliation":[{"name":"American University of Beirut","place":["Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi","family":"Sabra","sequence":"additional","affiliation":[{"name":"American University of Beirut","place":["Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charbel","family":"Massaad","sequence":"additional","affiliation":[{"name":"Sorbonne Paris Cite University","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Hamad Medical Corporation","place":["Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awad","family":"Rashid","sequence":"additional","affiliation":[{"name":"Hamad Medical Corporation","place":["Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Moodad","sequence":"additional","affiliation":[{"name":"American University of Beirut","place":["Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Block","sequence":"additional","affiliation":[{"name":"South Texas Veterans Healthcare System and the University of Texas Health Science Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Gorin","sequence":"additional","affiliation":[{"name":"South Texas Veterans Healthcare System and the University of Texas Health Science Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna E.","family":"Abboud","sequence":"additional","affiliation":[{"name":"South Texas Veterans Healthcare System and the University of Texas Health Science Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaad A.","family":"Eid","sequence":"additional","affiliation":[{"name":"American University of Beirut","place":["Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,11,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.02.025"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283451901"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906805106"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3313"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199701)247:1<9::AID-AR2>3.0.CO;2-W"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000251500.94478.18"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000187457.24338.3D"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.04.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.455782"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00653.x"},{"key":"e_1_3_3_13_2","first-page":"347","article-title":"Antisense oligonucleotides: Basic concepts and mechanisms","volume":"1","author":"Dias N","year":"2002","unstructured":"Dias N, and Stein CA. 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