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

Am J Pathol. 2023 Mar;193(3):275-285. doi: 10.1016/j.ajpath.2022.12.006. Epub 2022 Dec 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury* / genetics
  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Animals
  • Cell Polarity* / genetics
  • Cell Polarity* / physiology
  • Fibrosis / genetics
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Kidney* / metabolism
  • Kidney* / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / pathology
  • Ureteral Obstruction* / complications
  • Ureteral Obstruction* / genetics
  • Ureteral Obstruction* / metabolism
  • Ureteral Obstruction* / pathology