Zhang Chuyue, Li Wen, Wen Junkai, Yang Zhuo
School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
J Cell Mol Med. 2017 Jul;21(7):1315-1328. doi: 10.1111/jcmm.13061. Epub 2017 Feb 3.
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.
足细胞功能障碍导致的肾小球疾病占终末期肾病的90%。进化上保守的Notch信号通路在足细胞发育和功能中起关键作用。然而，Notch通路调节足细胞分化的潜在机制仍不太清楚。自噬在不同动物模型中被报道与Notch信号通路相关，被认为是足细胞分化过程中的一个可能参与者。在这里，我们发现Notch1的动态变化与自噬一致：它们在肾脏发育和足细胞分化过程中均增加。有趣的是，当用DAPT下调Notch信号时，自噬大大减少，分化也受到损害。此外，为了更好地理解Notch信号与自噬在足细胞分化中的关系，添加雷帕霉素以提高DAPT处理细胞中的自噬水平，结果，nephrin得以恢复，DAPT诱导的损伤得到改善。因此，我们提出自噬参与了由Notch信号调节的肾脏发育和足细胞分化。
