Autophagy gene atg7 regulates albumin transcytosis in renal tubule epithelial cells

Yushi Uchida, Kumiko Torisu, Kenji Ueki, Kazuhiko Tsuruya, Toshiaki Nakano, Takanari Kitazono

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)


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 (ATG7) knockdown HK-2 cells. Colocalization of FcRn with RAB7-positive late endosomes and RAB11-positive recycling endosomes was reduced in ATG7 knockdown cells, which decreased recycling of FcRn to the plasma membrane. In ATG7 or autophagy-related 5 (ATG5) knockdown cells and Atg5 or Atg7 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 ATG7 or ATG5 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.

ジャーナルAmerican Journal of Physiology - Renal Physiology
出版ステータス出版済み - 11月 2021

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 泌尿器学


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