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

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.

Long noncoding RNA nuclear enriched abundant transcript 1/miRNA-124 axis correlates with increased disease risk, elevated inflammation, deteriorative disease condition, and predicts decreased survival of sepsis

“…[22–25] For miR-124, some in vivo or in vitro experiments disclose that it may facilitate the suppression of inflammatory responses in sepsis. [14,15,26] For instance, a study discovers that miR-124 downregulation attenuates the PPARγ-mediated inhibition of pro-inflammatory cytokines in RAW264.7 cells. [15] Besides, a study discloses the decreased serum levels of TNF-α, IL-1β, and IL-6 in the sepsis mice treated with miR-124 mimics.…”

“…[15] Besides, a study discloses the decreased serum levels of TNF-α, IL-1β, and IL-6 in the sepsis mice treated with miR-124 mimics. [26] Also, another study shows that miR-124 attenuates production of inflammatory cytokines through targeting related genes of STAT3, TNF-α converting enzyme and acetylcholinesterase in LPS-induced sepsis mice and LPS-exposed cells. [14] These studies reveal that miR-124 may play a role in the anti-inflammatory mechanism of sepsis, and indicate that miR-124 may serve as a diagnostic or prognostic marker in sepsis, while the related evidence in clinical practice is rarely seen.…”

“…However, the relevant investigation was seldom reported. [9–11,14,15,26] Thus, we performed this study to explore the association of lnc-NEAT1 with miR-124, and further investigate the correlation of lnc-NEAT1/miR-124 axis with sepsis risk and severity, inflammatory cytokines levels as well as survival in patients with sepsis. We observed that lnc-NEAT1 expression was negatively associated with miR-124 expression in patients with sepsis as well as in HCs, and lnc-NEAT1/miR-124 axis correlated with elevated sepsis risk and severer disease condition, and predicted decreased survival in patients with sepsis.…”

Retracted: Quercetin alleviates lipopolysaccharide‐induced inflammatory responses by up‐regulation miR‐124 in human renal tubular epithelial cell line HK‐2

“…For example, miR‐124 was found to play an anticancer role and inhibit proliferation and migration of tumor cells, such as bladder cancer and lung cancer . In addition, the role of miR‐124 in kidney injury was gradually discovered, that miR‐124 reduced excessive inflammation and kidney damage in sepsis mice . Nevertheless, the function of miR‐124 in CKD stays exceedingly uninvestigated.…”

Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway

“…MiRNAs have been shown to be involved in a variety of biological processes, including sepsis-induced AKI. For example, miR-107, miR-124, miR-204 and miR-590 are mediators of sepsis-induced AKI for their ability to specifically bind to 3′-UTRs to inhibit translation of the target genes [21, 22]. In the present study, we aimed to investigate the role of miR-218-5p and its target gene HO-1 in sepsis-induced AKI and hypothesized that honokiol could ameliorate sepsis-induced AKI by targeting the miR-218-5p/HO-1 signaling pathway.…”