Deficiency of the Planar Cell Polarity Protein Intu Delays Kidney Repair and Suppresses Renal Fibrosis after Acute Kidney Injury.

Planar cell polarity (PCP), a process of coordinated alignment of cell polarity across the tissue plane, may contribute to the repair of renal tubules after kidney injury. Intu is a key effector protein of PCP. Herein, conditional knockout (KO) mouse models that ablate Intu specifically from kidney tubules (Intu KO) were established. Intu KO mice and wild-type littermates were subjected to unilateral renal ischemia/reperfusion injury (IRI) or unilateral ureteral obstruction. Kidney repair was evaluated by histologic, biochemical, and immunohistochemical analyses. In vitro, scratch wound healing was examined in Intu-knockdown and control renal tubular cells. Ablation of Intu in renal tubules delayed kidney repair and ameliorated renal fibrosis after renal IRI. Intu KO mice had less renal fibrosis during unilateral ureteral obstruction. Mechanistically, Intu KO kidneys had less senescence but higher levels of cell proliferation and apoptosis during kidney repair after renal IRI. In vitro, Intu knockdown suppressed scratch wound healing in renal tubular cells, accompanied by the abnormality of centrosome orientation. Together, the results provide the first evidence for the involvement of PCP in tubular repair after kidney injury, shedding light on new strategies for improving kidney repair and recovery. Copyright © 2023 American Society for Investigative Pathology. All rights reserved.

Citation

Shixuan Wang, Aimin Liu, Yunchao Su, Zheng Dong. Deficiency of the Planar Cell Polarity Protein Intu Delays Kidney Repair and Suppresses Renal Fibrosis after Acute Kidney Injury. The American journal of pathology. 2023 Mar;193(3):275-285

Mesh Tags

PMID: 36586478

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