Abstract: TH-OR113

MicroRNA-214 Confers the Pathogenesis of CKD by Disrupting the Mitochondrial OXPHOS

Session Information

  • Scarred for Life?
    November 02, 2017 | Location: Room 394, Morial Convention Center
    Abstract Time: 05:30 PM - 05:42 PM

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Zhang, Aihua, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Bai, Mi, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Zhang, Yue, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Huang, Songming, Children's Hospital of Nanjing Medical University, Nanjing, China
  • Jia, Zhanjun, Children's Hospital of Nanjing Medical University, Nanjing, China
Background

Mitochondria are critical in determining the energy hemostasis and cell fate. Mitochondrial dysfunction (MtD) presenting with aberrant mitochondrial oxidative phosphorylation (OXPHOS) and other abnormalities is involved in the chronic kidney disease (CKD). Here we investigated the role of miR-214 in mediating the MtD and kidney injury in CKD.

Methods

The CKD patients’ renal biopsy tissues, three CKD animal models (UUO, albumin-overload, and post-AKI), and tubular cells challenged with several insults were used to define the role of miR-214 in CKD, as well as the potential mechanisms.

Results

In CKD patients, the renal tubules presented more abundant miR-214 expression compared with the healthy controls, which was accompanied by a positive correlation with the severity of proteinuria and renal fibrosis. Meanwhile, several lines of CKD animal model of UUO, albumin-overload, and post-AKI and renal tubular cell models induced by IL-1β, hypoxia, albumin, or TGF-β displayed similar enhancement of miR-214. Importantly, systemic inhibition or specific tubular deletion of miR-214 strikingly attenuated CKD pathology in line with the ameliorated responses of apoptosis, inflammation, and fibrosis in CKD models mentioned above. In contrast, overexpressing miR-214 induced tubular cell apoptosis. Moreover, in the mechanistic study, we proved that cytoplasm miR-214 could be translocated into the mitochondria to target mitochondrial gene ND4L and ND6 to disrupt mitochondrial OXPHOS, leading to mitochondrial dysfunction and subsequent tubular injury and fibrosis in CKDs.

Conclusion

These results not only demonstrated a pathogenic role of miR-214 in CKDs by targeting mitochondrial gene ND4L and ND6 to disrupt mitochondrial OXPHOS but also suggested the potential of this microRNA as the therapeutic target and diagnostic biomarker of CKDs.