Downregulation of miR-527 alleviates sepsis-induced acute kidney injury via targeting Beclin1

• Ke Xu ^[2] ; Xiaojun Mo ^[2] ; Yijun Wang ^[2] ; Zhenhua Zeng ^[1] ; Ziqiang Xu ^[2] ; Dongyou Yue ^[2] ; Guicheng Li ^[2] ; Tao Li ^[2] ; Junhong Liu ^[2] ; Jiemin Yuan ^[2]
  1. [1] Southern Medical University

     Southern Medical University

     China

     
  2. [2] First People's Hospital of Chenzhou, Chenzhou, Hunan, China.
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 38, Nº. 4, 2023, págs. 443-452
• Idioma: inglés
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• Resumen

  • Background. Sepsis-induced acute kidney injury (AKI) is known to result from the inflammatory responses. MiRNAs participate in the development of sepsis-induced AKI. Nevertheless, the function of miR527 in sepsis-induced AKI remains unclear.

    Methods. Cell viability was evaluated by CCK8 assay, and TUNEL staining was applied to assess cell apoptosis. Pro-inflammatory cytokine (TNF-α, IL-6 and IL-1β) levels were evaluated by ELISA. Meanwhile, the relation among miR-527 and Beclin1 was detected by dual luciferase report assay. Western blot and RT-qPCR were used to examine the protein and mRNA levels, respectively. Furthermore, an in vivo model was constructed to assess the function of miR-527 in sepsisinduced AKI.

    Results. MiR-527 downregulation significantly alleviated the symptoms of sepsis-induced AKI in mice.

    MiR-527 level in HK-2 cells was significantly upregulated by LPS, and downregulation of miR-527 notably reversed LPS-induced inhibition of HK-2 cell viability by inhibiting apoptosis. In addition, LPS greatly increased TNF-α, IL-6 and IL-1β levels in supernatant of HK-2 cells, while miR-527 inhibitor partially restored this phenomenon. Meanwhile, Beclin1 was found to be the downstream mRNA of miR-527, and miR-527 inhibitor notably upregulated the level of LC3. MiR-527 downregulation reversed LPS-induced HK-2 cell injury through suppression of TGF-β pathway.

    Conclusion. Downregulation of miR-527 alleviated sepsis-induced AKI via targeting Beclin1. Thus, miR527 might act as a vital mediator in sepsis-induced AKI.