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Kidney Week

Abstract: FR-PO175

Intu Deficiency in Renal Tubules Delays Kidney Repair yet Suppresses Renal Fibrosis After Kidney Injury

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Wang, Shixuan, Augusta University, Augusta, Georgia, United States
  • Dong, Zheng, Augusta University, Augusta, Georgia, United States
Background

Intu is an effector protein of the planar cell polarity network that is essential for embryonic development and maintenance of normal organ functions. It was recently demonstrated that Intu plays a protective role in renal ischemia/reperfusion injury via interacting partner Stat1. However, the role of Intu in kidney repair and fibrosis remains unknown.

Methods

We have established an inducible Intu knockout mouse model that was exposed to doxycycline to ablate Intu specifically from kidney tubules (iRT-Intu-KO). iRT-Intu-KO mice and wild-type littermates were subjected to unilateral renal ischemia/reperfusion or ureteral obstruction injury. Kidney repair/recovery was evaluated by histological, biochemical, immunohistochemical and immunofluorescence approaches. In vitro, we examined Intu-knockdown proximal tubular cells.

Results

We found that ablation of Intu in renal tubules delayed kidney recovery and ameliorated renal fibrosis after renal ischemia/reperfusion injury. These mice also had less renal fibrosis during unilateral ureteral obstruction. We further found that senescence was suppressed while cell proliferation was increased in Intu knockout kidneys following renal ischemia/reperfusion injury. In cultured renal tubular cells, knockdown of Intu inhibited cell migration, accompanied by the abnormality of centrosome orientation.

Conclusion

Knockout of Intu suppressed kidney recovery and weakened fibrosis, associated with centrosome orientation abnormality and senescence inhibition. These findings suggest that planar cell polarity may contribute to tubular repair after kidney injury, shedding light on new strategies for improving kidney repair and recovery.

Funding

  • NIDDK Support