title: Loss of miR-125b contributes to upregulation of CYP24 in uraemic rats.
abstract: OBJECTIVE
  Abnormal upregulation of CYP24 contributes to vitamin D insufficiency and resistance to vitamin D therapy in chronic kidney disease (CKD), because human CYP24 is a key enzyme involved in the inactivation of 1a,25-dihydroxyvitamin D3 (1a,25(OH)2D3; calcitriol) and 1,25(OH)2D3. There are multiple mechanisms regulating CYP24 in a variety of types of tissues and diseases. An increasing body of evidence suggests that microRNA-125b (miR-125b) plays an important role in post-transcriptional regulation of CYP24 mRNA.
  
  
  METHODS
  We sought to test hypothesis that abnormal elevation of CYP24 in CKD is a consequence of loss of miR-125b in CKD in a uraemia rat model.
  
  
  RESULTS
  We found that expression of miR-125b was significantly inhibited in uraemic rats coupled with increased CYP24 at both protein and mRNA levels compared with normal controls. In NRK-52 kidney cells, we further found that miR-125b antagomirs increased CYP24 but miR-125b mimics decreased CYP24, and luciferase assay confirmed that CYP24 is a direct target of miR-125b. Vitamin D status exerted no significant effects on expression of both miR-125b and CYP24 in uraemic rats.
  
  
  CONCLUSIONS
  These results suggest that modulation of miR-125b may be used for treatment of Vitamin D insufficiency in CKD.
authors.affiliation: Division of Blood Purification, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Blood Purification, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Division of Blood Purification, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Blood Purification, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Gao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation; D007668:Kidney / Q000201:enzymology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000201:enzymology* / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation; D014511:Uremia / Q000201:enzymology* / Q000235:genetics; D014808:Vitamin D Deficiency / Q000201:enzymology / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C581261:MIRN125 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; C585551:Cyp24a1 protein, rat; D065668:Vitamin D3 24-Hydroxylase
keywords: CYP24; chronic kidney disease; miR-125b; vitamin D