{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:47:58Z","timestamp":1789984078485,"version":"4.0.1"},"reference-count":36,"publisher":"Portland Press Ltd.","issue":"4","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":330,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8,31]]},"abstract":"<jats:p>Two coding sequence variants (G1 and G2) of Apolipoprotein L1 (APOL1) gene have been implicated as a higher risk factor for chronic kidney diseases (CKD) in African Americans when compared with European Americans. Previous studies have suggested that the APOL1 G1 and G2 variant proteins are more toxic to kidney cells than the wild-type APOL1 G0, but the underlying mechanisms are poorly understood. To determine whether endoplasmic reticulum (ER) stress contributes to podocyte toxicity, we generated human podocytes (HPs) that stably overexpressed APOL1 G0, G1, or G2 (Vec\/HPs, G0\/HPs, G1\/HPs, and G2\/HPs). Propidium iodide staining showed that HP overexpressing the APOL1 G1 or G2 variant exhibited a higher rate of necrosis when compared with those overexpressing the wild-type G0 counterpart. Consistently, the expression levels of nephrin and podocin proteins were significantly decreased in the G1- or G2-overexpressing cells despite the maintenance of their mRNA expressions levels. In contrast, the expression of the 78-kDa glucose-regulated protein ((GRP78), also known as the binding Ig protein, BiP) and the phosphorylation of the eukaryotic translation initiation factor 1 (eIF1) were significantly elevated in the G1\/HPs and G2\/HPs, suggesting a possible occurrence of ER stress in these cells. Furthermore, ER stress inhibitors not only restored nephrin protein expression, but also provided protection against necrosis in G1\/HPs and G2\/HPs, suggesting that APOL1 risk variants cause podocyte injury partly through enhancing ER stress.<\/jats:p>","DOI":"10.1042\/bsr20171713","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T14:16:32Z","timestamp":1530540992000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["APOL1 risk variants cause podocytes injury through enhancing endoplasmic reticulum stress"],"prefix":"10.1042","volume":"38","author":[{"given":"Hongxiu","family":"Wen","sequence":"first","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqian","family":"Lan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Aging and Regenerative Medicine, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China"},{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh Shadafarin\u00a0Marashi","family":"Shoshtari","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith\u00a0M.","family":"Eng","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory for Aging and Regenerative Medicine, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Aging and Regenerative Medicine, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichao","family":"Wang","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."},{"name":"Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Skorecki","sequence":"additional","affiliation":[{"name":"Nephrology and Molecular Medicine, Technion Institute of Technology and Rambam Medical Center, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou University Institute of Nephrology, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guisheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Aging and Regenerative Medicine, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huairong","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory for Aging and Regenerative Medicine, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwani","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravin\u00a0C.","family":"Singhal","sequence":"additional","affiliation":[{"name":"Feinstein Institute for Medical Research and Hofstra Northwell Medical School, Manhasset, NY, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"2021111619025964200_B1","volume-title":"USRDS 2009 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States","author":"US Renal Data System","year":"2009"},{"key":"2021111619025964200_B2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nrneph.2015.216","article-title":"HIV-associated immune complex kidney disease","volume":"12","author":"Nobakht","year":"2016","journal-title":"Nat. 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