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In the initial stages of CaOx kidney stone formation, Randall's plaques (RPs) develop. Liver X receptors (LXRs) inhibit oxidative stress and in\ufb02ammatory in other diseases; nevertheless, the role of LXRs in nephrolithiasis has yet to be elucidated. In this study, the role of LXRs in the progression of RP formation was investigated. Microarray analysis revealed that LXR\/RXR levels were significantly greater in low\u2010plaque tissues (&lt;5%) than in high\u2010plaque tissues (&gt;5%), confirming the link between LXR activation and RP formation. Correspondingly, expression levels of two LXR target genes, LXR\u03b1 and LXR\u03b2, were lower in high\u2010plaque tissues than in low\u2010plaque tissues. In vitro, LXR agonist alleviated calcium oxalate monohydrate\u2010induced cellular calcium deposits and apoptosis. LXR activation decreased reactive oxygen species production and gene expression of inflammatory mediators, including osteopontin that has recently been demonstrated to correlate with the development of RPs. Moreover, p38 MAPK and JNK signaling may mediate LXR\u2010regulated expression in HK\u20102 cells. In an animal model, the deposition was reduced by activating LXR, and osteopontin expression was also inhibited. Our findings suggest a role for LXRs in the progression of idiopathic CaOx kidney stones; LXR agonists may have therapeutic potential for the treatment of nephrolithiasis.<\/jats:p>","DOI":"10.1002\/jcp.28101","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T03:01:12Z","timestamp":1547002872000},"page":"14109-14122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Activation of liver X receptor suppresses osteopontin expression and ameliorates nephrolithiasis"],"prefix":"10.1002","volume":"234","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Urology Shanghai Changzheng Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Shanghai Changzheng Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Fei","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Urology Shanghai Changzheng Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Urology Shanghai Changzheng Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010lin","family":"Mei","sequence":"additional","affiliation":[{"name":"Division of Nephrology Shanghai Changzheng Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6057-4645","authenticated-orcid":false,"given":"Xiao\u2010Jing","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Shanghai Changzheng Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.860"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(02)00030-0"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213071200"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-010-0271-8"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.723"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.09.015"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000238"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116755"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(00)00108-6"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000206"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2012.03.013"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm820"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112059299"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.6.985"},{"issue":"1","key":"e_1_2_7_1_16_1","first-page":"89","article-title":"Experimental calcium oxalate nephrolithiasis and the formation of human urinary stones","volume":"9","author":"Khan S. 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