In their recently published paper in Nature Communications, Aurore Claude-Taupin et al.
explore the critical role of shear stress, a known regulator of renal function, and its dysregulation in various kidney diseases.
Building on prior research highlighting the significance of primary cilium-dependent autophagy in kidney epithelial cells' response to fluid flow, a new dimension has emerged.Key Insights
- Nuclear YAP/TAZ's involvement in negatively regulating autophagy flux in response to fluid flow in kidney epithelial cells.
- This crosstalk is facilitated by primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway.
- Validation of the YAP/TAZ-autophagy molecular dialog in in vivo models including a zebrafish model of kidney development and a mouse model of unilateral ureteral obstruction.
- In vitro assay replicating accelerated flow in early chronic kidney disease (CKD) stages activates YAP, leading to a primary cilium-dependent inhibition of autophagic flux.
- Confirmation of the YAP/autophagy relationship in renal biopsies from patients with diabetic kidney disease (DKD), the primary cause of CKD.
The findings shed light on the pivotal roles of YAP/TAZ and autophagy in translating fluid flow into cellular and physiological responses, providing valuable insights into the molecular mechanisms of kidney diseases.
Read the full article here: https://lnkd.in/g673vuZh