{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:28:43Z","timestamp":1790789323424,"version":"4.1.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8170101445"],"award-info":[{"award-number":["8170101445"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["7182191"],"award-info":[{"award-number":["7182191"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010270","name":"Capital Health Research and Development of Special","doi-asserted-by":"crossref","award":["2016-2-2242"],"award-info":[{"award-number":["2016-2-2242"]}],"id":[{"id":"10.13039\/501100010270","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:p> Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-\u03b1 gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-\u03b1 by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis. <\/jats:p>","DOI":"10.1152\/ajprenal.00132.2020","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T16:00:49Z","timestamp":1594051249000},"page":"F202-F214","source":"Crossref","is-referenced-by-count":25,"title":["MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA"],"prefix":"10.1152","volume":"319","author":[{"given":"Boxing","family":"Su","sequence":"first","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyue","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3068365"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2877-x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00064"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003205"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni178"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-017-2048-0"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.020"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912701107"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75852"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P040501"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-008-0143-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14078"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090594"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3762"},{"key":"B15","first-page":"256","volume":"3","author":"Khan SR","year":"2014","journal-title":"Transl Androl Urol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.8"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2010.04.065"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature04303"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000096065.61481.35"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8306736"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00482.2011"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-013-3085-y"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2312"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5833"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav1741"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00211.2016"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.7150\/thno.29832"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw077"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-005-0477-3"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2018.06.013"},{"key":"B31","first-page":"e86","volume":"12","author":"Romero V","year":"2010","journal-title":"Rev Urol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370918"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1159\/000113489"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00790"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-13-206"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9605890"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/01.mnh.0000447017.28852.52"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2007.01953.x"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510565103"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101306"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1159\/000343452"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.02.010"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7150\/thno.33482"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2016.08.007"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00132.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T13:12:37Z","timestamp":1595250757000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajprenal.00132.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,1]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,8,1]]}},"alternative-id":["10.1152\/ajprenal.00132.2020"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00132.2020","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,1]]}}}