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Article

miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis

  • Authors:
    • Xiao‑Yue Li
    • Yu‑Qi Zhang
    • Gang Xu
    • Shao‑Hong Li
    • Heng Li
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guanxi 541199, P.R. China, Department of Geriatrics, Guangzhou First People's Hospital, Guangzhou, Guangdong 510000, P.R. China, Department of Emergency, TungWah Affiliated Hospital of Sun Yat‑sen University, Dongguan, Guangdong 523220, P.R. China, Department of Cardiovascular Medicine, TungWah Affiliated Hospital of Sun Yat‑sen University, Dongguan, Guangdong 523220, P.R. China
  • Pages: 3468-3476
    |
    Published online on: March 13, 2018
       https://doi.org/10.3892/ijmm.2018.3564
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Abstract

Previous studies have indicated that monocyte chemoattractant protein-1 (MCP‑1), also referred to as C‑C motif chemokine ligand 2, has a significant role in the pathogenesis of sepsis, however, how microRNAs (miRs) contribute to this process remains to be fully elucidated. In the present study, using a mouse model of disseminated candidiasis, the renoprotective effect of itraconazole (ITR) and adenovirus‑delivered miR‑124 was investigated. The mice were treated with ITR (50 mg/kg) or transfected with miR‑124 mimics via tail‑vein injection 7 days prior to Candida albicans infection. The survival outcome was monitored following candidiasis‑induced sepsis with ITR or miR‑124 mimics treatment. The levels of pro‑inflammatory cytokines, including tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and IL‑6, were determined using enzyme‑linked immunosorbent assays. The mRNA and protein levels were assayed using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The results showed that ITR and miR‑124 mimics improved the survival outcome in candidiasis‑induced septic mice. The findings also indicated a significant downregulation in the serum levels of TNF‑α, IL‑1β and IL‑6 in the septic mice treated with ITR or miR‑124 mimics. Of note, ITR treatment significantly increased the expression of miR‑124 and decreased the levels of MCP‑1 in the kidneys of the septic mice. It was also shown that the overexpression of miR‑124 reduced the expression of MCP‑1 and attenuated candidiasis‑induced acute kidney injury (AKI) in septic mice. Transfection with miR‑124 mimics was equivalent to ITR in reducing the excessive inflammatory response and renal lesions in septic mice. These results provided evidence supporting the use of miR‑124 mimics as a therapeutic approach for attenuating candidiasis-induced AKI.
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Copy and paste a formatted citation
Spandidos Publications style
Li XY, Zhang YQ, Xu G, Li SH and Li H: miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis. Int J Mol Med 41: 3468-3476, 2018.
APA
Li, X., Zhang, Y., Xu, G., Li, S., & Li, H. (2018). miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis. International Journal of Molecular Medicine, 41, 3468-3476. https://doi.org/10.3892/ijmm.2018.3564
MLA
Li, X., Zhang, Y., Xu, G., Li, S., Li, H."miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis". International Journal of Molecular Medicine 41.6 (2018): 3468-3476.
Chicago
Li, X., Zhang, Y., Xu, G., Li, S., Li, H."miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis". International Journal of Molecular Medicine 41, no. 6 (2018): 3468-3476. https://doi.org/10.3892/ijmm.2018.3564
Copy and paste a formatted citation
x
Spandidos Publications style
Li XY, Zhang YQ, Xu G, Li SH and Li H: miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis. Int J Mol Med 41: 3468-3476, 2018.
APA
Li, X., Zhang, Y., Xu, G., Li, S., & Li, H. (2018). miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis. International Journal of Molecular Medicine, 41, 3468-3476. https://doi.org/10.3892/ijmm.2018.3564
MLA
Li, X., Zhang, Y., Xu, G., Li, S., Li, H."miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis". International Journal of Molecular Medicine 41.6 (2018): 3468-3476.
Chicago
Li, X., Zhang, Y., Xu, G., Li, S., Li, H."miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis". International Journal of Molecular Medicine 41, no. 6 (2018): 3468-3476. https://doi.org/10.3892/ijmm.2018.3564
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