Autophagy gene ATG7 regulates albumin transcytosis in renal tubule epithelial cells.

Abstract

Receptor-mediated albumin transport in proximal tubule epithelial cells (PTECs) is important to control proteinuria. Autophagy is an evolutionarily conserved degradation pathway and its role in intracellular trafficking through interaction with the endocytic pathway has recently been highlighted. Here, we determined whether autophagy regulates albumin transcytosis in PTECs and suppresses albumin-induced cytotoxicity using human proximal tubule (HK-2) cells. Neonatal Fc-receptor (FcRn), a receptor for albumin transcytosis, partially co-localized with autophagosomes. Recycling of FcRn was attenuated and FcRn accumulated in autophagy related 7 (ATG7) knockdown HK-2 cells. Co-localization of FcRn with RAB7-positive late endosomes and RAB11-positive recycling endosomes was reduced in ATG7 knockdown cells, resulting in decreased recycling of FcRn to the plasma membrane. In ATG7 knockdown cells, albumin transcytosis was significantly reduced and intracellular albumin accumulation was increased. Finally, release of KIM-1, a marker of tubule injury, from ATG7 knockdown cells was increased in response to excess albumin. In conclusion, suppression of autophagy in tubules impairs FcRn transport, thereby inhibiting albumin transcytosis. The resulting accumulation of albumin induces cytotoxicity in tubules.