自噬
纤毛
细胞生物学
肾
肾脏疾病
安普克
生物
化学
癌症研究
内分泌学
细胞凋亡
磷酸化
生物化学
蛋白激酶A
作者
Aurore Claude-Taupin,Pierre Isnard,Alessia Bagattin,Nicolas Kuperwasser,Federica Roccio,Biagina Ruscica,Nicolas Goudin,Meriem Garfa-Traoré,Alice Regnier,Lisa Turinsky,Martine Burtin,Marc Foretz,Marco Pontoglio,Étienne Morel,Benoı̂t Viollet,Fabiola Terzi,Patrice Codogno,Nicolas Dupont
标识
DOI:10.1038/s41467-023-43775-1
摘要
Abstract Shear stress generated by urinary fluid flow is an important regulator of renal function. Its dysregulation is observed in various chronic and acute kidney diseases. Previously, we demonstrated that primary cilium-dependent autophagy allows kidney epithelial cells to adapt their metabolism in response to fluid flow. Here, we show that nuclear YAP/TAZ negatively regulates autophagy flux in kidney epithelial cells subjected to fluid flow. This crosstalk is supported by a primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway. We confirm the relevance of the YAP/TAZ-autophagy molecular dialog in vivo using a zebrafish model of kidney development and a unilateral ureteral obstruction mouse model. In addition, an in vitro assay simulating pathological accelerated flow observed at early stages of chronic kidney disease (CKD) activates YAP, leading to a primary cilium-dependent inhibition of autophagic flux. We confirm this YAP/autophagy relationship in renal biopsies from patients suffering from diabetic kidney disease (DKD), the leading cause of CKD. Our findings demonstrate the importance of YAP/TAZ and autophagy in the translation of fluid flow into cellular and physiological responses. Dysregulation of this pathway is associated with the early onset of CKD.
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