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Deficiency of the Planar Cell Polarity Protein Intu Delays Kidney Repair and Suppresses Renal Fibrosis after Acute Kidney Injury.
- Source :
-
The American journal of pathology [Am J Pathol] 2023 Mar; Vol. 193 (3), pp. 275-285. Date of Electronic Publication: 2022 Dec 28. - Publication Year :
- 2023
-
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.<br /> (Copyright © 2023 American Society for Investigative Pathology. All rights reserved.)
- Subjects :
- Animals
Mice
Fibrosis genetics
Fibrosis metabolism
Fibrosis pathology
Kidney Tubules metabolism
Kidney Tubules pathology
Mice, Inbred C57BL
Mice, Knockout
Acute Kidney Injury genetics
Acute Kidney Injury metabolism
Acute Kidney Injury pathology
Cell Polarity genetics
Cell Polarity physiology
Kidney metabolism
Kidney pathology
Reperfusion Injury genetics
Reperfusion Injury metabolism
Reperfusion Injury pathology
Ureteral Obstruction complications
Ureteral Obstruction genetics
Ureteral Obstruction metabolism
Ureteral Obstruction pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 193
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 36586478
- Full Text :
- https://doi.org/10.1016/j.ajpath.2022.12.006