{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:29:08Z","timestamp":1785472148780,"version":"3.56.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T00:00:00Z","timestamp":1540512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570623"],"award-info":[{"award-number":["81570623"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["GJYQ-1404"],"award-info":[{"award-number":["GJYQ-1404"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    MLKL is a central mediator for necroptosis. Its knockout significantly relieves acute kidney injury (AKI). However, its upstream regulatory mechanism in AKI has not been fully elucidated. We recently reviewed how microRNAs (miRNAs), a type of well\u2010studied epigenetic regulator, play critical roles in AKI. Here, we evaluated miRNAs that potentially target MLKL and evaluated their function in human tubular epithelial cells in response to toxic and ischemic insults. TargetScan analysis showed that miR\u2010194\u20105P, miR\u2010338\u20103P, miR\u2010500a\u20103P, and miR\u2010577 had MLKL binding sites. Although all 4 miRNAs are reduced in AKI, our data show that only hsa\u2010miR\u2010500a\u20103P was significantly suppressed in cisplatin\u2010treated human tubular epithelial (HK2) cells. We further found that hsa\u2010miR\u2010500a\u20103P alleviated cisplatin\u2010induced HK2 cell death, which was confirmed by transmission electron microscopy and flow cytometry. In addition, overexpression of hsa\u2010miR\u2010500a\u20103P decreased kidney injury molecule\u20101 mRNA and protein levels. Real\u2010time PCR, ELISA, and immunofluorescence data show that hsa\u2010miR\u2010500a\u20103P protected against inflammatory response, evidenced by decreased monocyte chemotactic protein\u20101 and proinflammatory cytokines TNF\u2010\u03b1 and IL\u20108. Further, hsa\u2010miR\u2010500a\u20103P attenuated P65 NF\u2010\u03baB phosphorylation and promoter activity. Mechanistically, luciferase reporter assay showed that hsa\u2010miR\u2010500a\u20103P bound the 3\u2032UTR of MLKL, thereby suppressing phosphorylation and membrane translocation of MLKL. In agreement with these findings, we identified that overexpression of hsa\u2010miR\u2010500a\u20103P attenuated cell injury and the inflammatory response in response to sodium azide treatment in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model. Results show that circulating exosomes from patients with AKI down\u2010regulated miR\u2010500a\u20103P, which suppressed cell injury and inflammation in HK2 cells. hsa\u2010miR\u2010500a\u20103P alleviated toxic and ischemic insults that were triggered by cell necroptosis and the inflammatory response in human HK2 cells by targeting MLKL. This may serve as a novel therapeutic target for treatment of AKI.\u2014Jiang, L., Liu, X.\u2010Q., Ma, Q., Yang, Q., Gao, L., Li, H.\u2010D., Wang, J.\u2010N., Wei, B., Wen, J., Li, J., Wu, Y.\u2010G., Meng, X.\u2010M. hsa\u2010miR\u2010500a\u20103P alleviates kidney injury by targeting MLKL\u2010mediated necroptosis in renal epithelial cells. FASEB J. 33, 3523\u20133535 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801711r","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T14:05:47Z","timestamp":1540562747000},"page":"3523-3535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["hsa\u2010miR\u2010500a\u20103P alleviates kidney injury by targeting MLKL\u2010mediated necroptosis in renal epithelial cells"],"prefix":"10.1096","volume":"33","author":[{"given":"Ling","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital Anhui Medical University  Hefei China"},{"name":"School of Pharmacy Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital Anhui Medical University  Hefei China"},{"name":"School of Pharmacy Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuying","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei 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Anti-inflammatory and Immune Medicine Ministry of Education  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei China"},{"name":"Anhui Institute of Innovative Drugs Anhui Medical University  Hefei China"},{"name":"The Key Laboratory of Major Autoimmune Diseases Anhui Medical University  Hefei China"},{"name":"Key Laboratory of Anti-inflammatory and Immune Medicine Ministry of Education  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Gui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei China"},{"name":"Anhui Institute of Innovative Drugs Anhui Medical University  Hefei China"},{"name":"The Key Laboratory of Major Autoimmune Diseases Anhui Medical University  Hefei China"},{"name":"Key Laboratory of Anti-inflammatory and Immune Medicine Ministry of Education  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014080741"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-052016-100247"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10274"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2883"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.37"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2015.10.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.450"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305538110"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012121169"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","unstructured":"Ren G. 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