Deficiency of the planar cell polarity protein intu delays kidney repair and suppresses renal fibrosis after acute kidney injury.
Deficiency of the planar cell polarity protein intu delays kidney repair and suppresses renal fibrosis after acute kidney injury.
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DOI：
10.1016/j.ajpath.2022.12.006
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Shixuan Wang;Aimin Liu;Yunchao Su;Z. Dong
中科院分区：
文献类型：
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作者：
Shixuan Wang;Aimin Liu;Yunchao Su;Z. Dong
平面细胞极性（PCP）是跨组织平面细胞极性协调排列的过程，可能有助于肾损伤后肾小管的修复。 Intu 是 PCP 的关键效应蛋白。在此，建立了从肾小管特异性消融IntuKO（IntuKO）的条件敲除（KO）小鼠模型。IntuKO小鼠和野生型同窝小鼠遭受单侧肾缺血/再灌注损伤（IRI）或单侧输尿管梗阻。通过组织学、生化和免疫组织化学分析评估肾脏修复。在体外，在 Intu 敲低和对照肾小管细胞中检查划痕伤口愈合。 Intuin肾小管的消融延迟了肾IRI后的肾脏修复并改善了肾纤维化。IntuKO小鼠在单侧输尿管梗阻期间的肾纤维化较少。从机制上讲，IntuKO肾脏在肾IRI后的肾脏修复过程中衰老较少，但细胞增殖和凋亡水平较高。在体外，Intuknockdown抑制肾小管细胞划痕愈合，并伴有中心体方向异常。总之，这些结果为 PCP 参与肾损伤后肾小管修复提供了第一个证据，为改善肾脏修复和恢复的新策略提供了线索。
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 ablateIntuspecifically from kidney tubules (IntuKO) were established.IntuKO 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 inIntu-knockdown and control renal tubular cells. Ablation ofIntuin renal tubules delayed kidney repair and ameliorated renal fibrosis after renal IRI.IntuKO mice had less renal fibrosis during unilateral ureteral obstruction. Mechanistically,IntuKO kidneys had less senescence but higher levels of cell proliferation and apoptosis during kidney repair after renal IRI.In vitro,Intuknockdown 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.