期刊
CELL DEATH & DISEASE
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-019-1933-2
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资金
- National Key Research and Development Program of China [2016YFC1305402]
- National Natural Science Foundation of China [81870492, 81900699, 81270782]
- Research Project of Science and Technology Commission of Shanghai Municipality [15140902800]
- Key Projects of National Basic Research Program of China 973 [2012CB517701]
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/EBP alpha in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBP alpha was selectively deleted in podocytes and by overexpressing C/EBP alpha 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/EBP alpha 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/EBP alpha as a new potential target in kidney aging.
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