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- Title
C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice.
- Authors
Zhang, Liwen; Zhou, Fangfang; Yu, Xialian; Zhu, Yufei; Zhou, Ying; Liu, Jian; Liu, Yunzi; Ma, Qingyang; Zhang, Yuchao; Wang, Weiming; Chen, Nan
- Abstract
Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of C/EBPα in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPα was selectively deleted in podocytes and by overexpressing C/EBPα in cultured podocytes, in which premature senescence was induced by treatment with adriamycin. Moreover, we illuminated the mechanisms by which podocyte senescence causes tubular impairment by stimulating HK-2 cells with bovine serum albumin (BSA) and chloroquine. Our findings suggest that C/EBPα knockout in podocytes aggravates podocyte senescence through the AMPK/mTOR pathway, leading to glomerulosclerosis, and that subsequent albuminuria exacerbates the epithelial–mesenchymal transdifferentiation of senescent tubular cells by suppressing autophagy. These observations highlight the importance of C/EBPα as a new potential target in kidney aging.
- Publication
Cell Death & Disease, 2019, Vol 10, Issue 10, pN.PAG
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-019-1933-2