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Citations to this article

KLF4-dependent epigenetic remodeling modulates podocyte phenotypes and attenuates proteinuria
Kaori Hayashi, … , Yusuke Sakamaki, Hiroshi Itoh
Kaori Hayashi, … , Yusuke Sakamaki, Hiroshi Itoh
Published May 8, 2014
Citation Information: J Clin Invest. 2014;124(6):2523-2537. https://doi.org/10.1172/JCI69557.
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Research Article Nephrology Article has an altmetric score of 24

KLF4-dependent epigenetic remodeling modulates podocyte phenotypes and attenuates proteinuria

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Abstract

The transcription factor Kruppel-like factor 4 (KLF4) has the ability, along with other factors, to reprogram somatic cells into induced pluripotent stem (iPS) cells. Here, we determined that KLF4 is expressed in kidney glomerular podocytes and is decreased in both animal models and humans exhibiting a proteinuric. Transient restoration of KLF4 expression in podocytes of diseased glomeruli in vivo, either by gene transfer or transgenic expression, resulted in a sustained increase in nephrin expression and a decrease in albuminuria. In mice harboring podocyte-specific deletion of Klf4, adriamycin-induced proteinuria was substantially exacerbated, although these animals displayed minimal phenotypical changes prior to adriamycin administration. KLF4 overexpression in cultured human podocytes increased expression of nephrin and other epithelial markers and reduced mesenchymal gene expression. DNA methylation profiling and bisulfite genomic sequencing revealed that KLF4 expression reduced methylation at the nephrin promoter and the promoters of other epithelial markers; however, methylation was increased at the promoters of genes encoding mesenchymal markers, suggesting selective epigenetic regulation of podocyte gene expression. Together, these results suggest that KLF4 epigenetically modulates podocyte phenotype and function and that the podocyte epigenome can be targeted for direct intervention and reduction of proteinuria.

Authors

Kaori Hayashi, Hiroyuki Sasamura, Mari Nakamura, Tatsuhiko Azegami, Hideyo Oguchi, Yusuke Sakamaki, Hiroshi Itoh

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2009 Total
Citations: 3 6 5 8 5 7 9 5 4 4 6 1 1 64
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Citations to this article (64)

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