ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO925

The Role of miR-21/Wnt in the Development of Renal Tubulointerstitial Fibrosis Secondary to Aristolochic Acid Induced AKI

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Fang, Yi, Zhongshan Hospital, Fudan University, Shanghai, China
  • Kuang, Qing, Zhongshan Hospital, Fudan University, Shanghai, China
  • Wu, Sheng, Zhongshan Hospital, Fudan University, Shanghai, China
  • Xue, Ning, Zhongshan Hospital, Fudan University, Shanghai, China
Background

AKI is increasingly recognized as a cumulative risk factor for developing advanced CKD. However, the factors governing the underlying mechanisms remain unclear. Previously we have found that the development of tubulointerstitial fibrosis after AKI was accompanied with an overwhelmed activation of miR-21 and canonical Wnt signaling, while inhibiting miR-21 or silencing Wnt ligands could partially attenuate AKI to CKD transition.

Methods

To explore the interaction between miR-21 and Wnt/β-catenin signaling, we exam the effects of genetic absence or pharmacologic inhibition of miR-21 on the expression of Wnt/β-catenin signaling pathway.

Results

In miR-21-/- mice, or in wild type mice treated with anti-miR-21 oligos, a significant reduction of Wnt1 and Wnt4 canonical signaling was found in the renal tissue, with partially reversal of renal interstitial fibrosis. Although renal abundance of miR-21 remains unchanged either after inhibition or activation of Wnt/β-catenin signaling, down-regulation of β-catenin with early intervention of ICG-001, a typical β-catenin inhibitor was associated with significant attenuation in renal interstitial fibrosis, protein expression of genes coding extracellular matrix as well as the downstream genes of β-catenin. Moreover, inhibiting β-catenin within 24h after aristolochic acid administration, not at a late stage, also attenuated aristolochic acid induced apoptosis and inflammation.

Conclusion


In conclusion, these results suggest that inhibiting miR-21 and β--catenin signaling may be effective approaches to preventing AKI to CKD progression.