期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 21, 期 7, 页码 1315-1328出版社
WILEY
DOI: 10.1111/jcmm.13061
关键词
notch signalling; autophagy; differentiation; podocyte; renal development
资金
- National Natural Science Foundation of China [31271074]
- National Basic Research Program of China [2011CB944003]
- National Innovation Experiment Program for University Students
Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down-regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT-treated cells, and as a result, nephrin was recovered and DAPT-induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling.
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