| First Author | Zhang L | Year | 2019 |
| Journal | Cell Death Dis | Volume | 10 |
| Issue | 10 | Pages | 684 |
| PubMed ID | 31527620 | Mgi Jnum | J:296490 |
| Mgi Id | MGI:6467864 | Doi | 10.1038/s41419-019-1933-2 |
| Citation | Zhang L, et al. (2019) C/EBPalpha deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice. Cell Death Dis 10(10):684 |
| abstractText | 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/EBPalpha in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPalpha was selectively deleted in podocytes and by overexpressing C/EBPalpha 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/EBPalpha 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/EBPalpha as a new potential target in kidney aging. |
