Affordable Access

Publisher Website

miR-204/miR-211 downregulation contributes to Candidemia-induced kidney injuries via derepression of Hmx1 expression

Life Sciences
Publication Date
DOI: 10.1016/j.lfs.2014.03.010
  • Candidemia
  • Candida Albicans
  • Renal Function
  • Kidney Injuries
  • Hmx1
  • Microrna
  • Mir-204
  • Mir-211
  • Gene Expression Regulation
  • Renal Glomerular Filtration Rate (Gfr)
  • Serum Cystatin C (Cysc)
  • Serum β2-Microglobulin (β2-Mg)
  • Biology


Abstract Aims This study was aimed to exploit the role of heme oxygenase Hmx1 and the potential miRNA mechanisms in the kidney injuries induced by urinary tract infection by Candida species/Candidemia. Main methods We employed a mouse model of systemic Candidiasis by injection of the Candida albicans strain SC5314 into C57BL/6 mice. Kidney injuries were assessed by measuring serum cystatin C (CysC), serum β2-microglobulin (β2-MG) and blood urea nitrogen (BUN). Validation of miRNA target gene was conducted by luciferase reporter gene assay, Western blot analysis and real-time RT-PCR. Key findings We showed here that Candidemia caused significant downregulation of microRNAs miR-204 and miR-211. In sharp contrast, Hmx1 expression was remarkably upregulated, particularly at the protein level. Computational analysis predicted Hmx1 as a target gene for both miR-204 and miR-211 that share the same seed site sequence. We then experimentally validated the targeting relationship between miR-204/miR-211 and Hmx1, which explains the reciprocal changes of expression of miR-204/miR-211 and Hmx1 in Candidemia. Administration of miR-204/miR-211 mimics substantially downregulated Hmx1 and mitigated the severity of the kidney injuries induced by Candidemia, as reflected by improved renal glomerular filtration rate (GFR) determined by serum cystatin C (CysC), serum β2-microglobulin (β2-MG) and blood urea nitrogen (BUN). Knockdown of miR-204/miR-211 worsened while forced expression of miR-204/miR-211 ameliorated kidney injuries in mice with systemic Candidiasis. Significance Our findings indicate that miR-204/miR-211 downregulation accounts at least partially for the Hmx1 upregulation and the miR-204/miR-211–Hmx1 signaling axis may contribute to immune-suppression in the host thereby the Candidemia-induced kidney dysfunction.

There are no comments yet on this publication. Be the first to share your thoughts.