In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 14, No. 634 ( 2022-03-02)
Abstract:
The transition from acute kidney injury, characterized by intrinsic repair, to incomplete repair and chronic damage has been difficult to study. Here, Gupta and colleagues modeled the transition from intrinsic to incomplete repair using human kidney organoids. A single exposure to cisplatin resulted in intrinsic repair, with preserved tubular architecture and up-regulation of genes associated with homology-directed repair, including Fanconi anemia complementation group D2 ( FANCD2 ). However, with repeated cisplatin exposure, FANCD2 and RAD51 recombinase ( RAD51 ) were down-regulated, leading to incomplete repair. The DNA ligase IV inhibitor SCR7 increased FANCD2-mediated repair and ameliorated progression to chronic injury in the organoids, suggesting that targeting the FANCD2/RAD51 pathway may have potential to treat kidney disease.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abj4772
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
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