{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:23:57Z","timestamp":1773833037350,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Our previous studies showed that vitamin D receptor (VDR) depletion promotes lipopolysaccharide (LPS)\u2010induced acute kidney injury (AKI) in mice, and renal VDR is down\u2010regulated in AKI, but the mechanism of VDR down\u2010regulation is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nutritional vitamin D deficiency was induced by feeding mice a vitamin D\u2010deficient (VD\u2010D) diet. Mice were injected intraperitoneally with LPS (20\u00a0mg\/kg) to establish LPS\u2010induced AKI. Levels of VDR and miR\u2010122 were measured both in vivo and in vitro. The associations between VDR and miR\u2010122 were analysed by dual\u2010luciferase reporter assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with vitamin D\u2010sufficient (VD\u2010S) mice, VD\u2010D mice developed more severe renal injury following LPS challenge. LPS induced a dramatic decrease in VDR expression and marked induction of miR\u2010122 both in vivo and in vitro. Furthermore, miR\u2010122 hairpin inhibitor alleviated LPS\u2010induced VDR down\u2010regulation whereas miR\u2010122 mimic directly suppressed VDR expression in HK\u20102 cells. In luciferase reporter assays, miR\u2010122 mimic was able to suppress luciferase activity in 293T cells co\u2010transfected with a luciferase reporter that contains a putative miR\u2010122 target site from 3\u2032UTR of the VDR transcript, but not when this site was mutated. Moreover, miR\u2010122 mimic significantly blocked paricalcitol\u2010induced luciferase activity in 293T cells co\u2010transfected with a VDRE\u2010driven luciferase reporter, whereas miR\u2010122 hairpin inhibitor enhanced paricalcitol's activity to suppress PUMA and caspase 3 activation induced by LPS in HK\u20102 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, these studies provide evidence that miR\u2010122 directly targets VDR in renal tubular cells, which strongly suggest that miR\u2010122 up\u2010regulation in the kidney under LPS challenge contributes to kidney injury by down\u2010regulating VDR expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13547","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T06:29:21Z","timestamp":1617085761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MicroRNA\u2010122 contributes to lipopolysaccharide\u2010induced acute kidney injury via down\u2010regulating the vitamin D receptor in the kidney"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7143-7750","authenticated-orcid":false,"given":"Jinrong","family":"He","sequence":"first","affiliation":[{"name":"Department of Nephrology The Third Xiangya Hospital Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Biological Sciences The University of Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Third Xiangya Hospital Central South University Changsha 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