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


The Latest on Twitter

Kidney Week

Abstract: SA-PO116

IKKα Aggravates Renal Fibrosis by Positively Regulating the Wnt/β-Catenin Pathway

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Hao, Zhang, Nanjing Medical University, Nanjing, China

Acute kidney injury (AKI) with maladaptive repair is a major contribution to renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we have revealed that IKKα was involved in inhibiting inflammation and kidney regeneration.


By mating IKKα-floxed mice with Kap-Cre transgenic mice, mice with IKKα gene specifically ablated in renal tubular cells were created. After dorsal incision, the left renal pedicle was clamped with a micro vascular clamp for 45 min, while the sham-operated mice underwent the same treatment except clamping renal pedicle. We added TGF-β1 to the culture medium to establish the cell fibrosis model in human tubular epithelial cells.


The expression of IKKα was up-regulated in kidney tubular epithelium in mice models of unilateral ureteral obstruction and ischemic reperfusion injury. In addition, immunohistochemical staining showed IKKα renal expression positively correlated with the kidney fibrosis in chronic kidney diseases (CKD) patients. Futhermore, we generated a knockout mouse model with IKKα gene specifically deleted in renal tubules. These knockout mice were phenotypically normal at birth and had no significant defects in kidney morphology and function. Compared with controls, Kap-IKKα-/- mice decreased Wnt/β-catenin activation, serum creatinine and attenuated interstitial fibrosis at 14 days after ischemic reperfusion injury. In vitro, IKKα blocked the interaction of GSK-3β with β-catenin in TGF-β1-stimulated human tubular epithelial cells resulting in β-catenin nuclear translocation. Additionally, blocking IKKα by siRNA specifically suppressed β-catenin activation and profibrotic gene expression such as fibronectin and α-smooth muscle actin.


IKKα aggravates renal fibrogenesis by amplifying regulation of the Wnt/β-catenin signaling pathway which may provide a potential anti-fibrosis therapy target for chronic kidney diseases.