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Loss of miR‐125b contributes to upregulation of CYP24 in uraemic rats
Author(s) -
Wang Lihua,
Gao Zhiying,
Wang Lili,
Gao Yongning
Publication year - 2016
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.12714
Subject(s) - downregulation and upregulation , medicine , vitamin d and neurology , calcitriol , kidney disease , microrna , endocrinology , messenger rna , cancer research , biology , biochemistry , gene
Aim 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. Conclusion These results suggest that modulation of miR‐125b may be used for treatment of Vitamin D insufficiency in CKD.