Autophagy gene regulates albumin transcytosis in renal tubule epithelial cells.

Am J Physiol Renal Physiol

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Published: November 2021

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 interactions 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. The neonatal Fc receptor (FcRn), a receptor for albumin transcytosis, is partially colocalized with autophagosomes. Recycling of FcRn was attenuated, and FcRn accumulated in autophagy-related 7 () knockdown HK-2 cells. Colocalization of FcRn with RAB7-positive late endosomes and RAB11-positive recycling endosomes was reduced in knockdown cells, which decreased recycling of FcRn to the plasma membrane. In or autophagy-related 5 () knockdown cells and or knockout mouse embryonic fibroblasts, albumin transcytosis was significantly reduced and intracellular albumin accumulation was increased. Finally, the release of kidney injury molecule-1, a marker of tubule injury, from or 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. Albumin transport in proximal tubule epithelial cells (PTECs) is important to control proteinuria. The neonatal Fc receptor (FcRn), a receptor for albumin transcytosis, is partially colocalized with autophagosomes. Recycling of FcRn to the plasma membrane was decreased in autophagy-related 7 () knockdown cells. In addition, albumin transcytosis was decreased in or autophagy-related 5 () knockdown PTECs. Finally, release of kidney injury molecule-1 from or knockdown cells was increased in response to excess albumin.

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http://dx.doi.org/10.1152/ajprenal.00172.2021DOI Listing

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