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.00172.2021 | DOI Listing |
Cell Rep Med
November 2024
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
Biomater Res
August 2024
College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, China Agricultural University, Key Lab of Fruit and Vegetable Processing, Ministry of Agriculture and Rural Affairs, Beijing 100083, China.
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October 2024
Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan. Electronic address:
Cytotoxic metabolites originating from the peripheral circulation can induce central nervous system complications associated with diabetes. Since a large proportion of these metabolites bind to plasma albumin, mechanisms for transporting albumin-metabolite complexes into the brain exist under diabetic conditions. Secreted protein acidic and rich in cysteine (SPARC) is one of the vesicular transport receptors responsible for albumin transport.
View Article and Find Full Text PDFEpilepsia
September 2024
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.
Stroke is a major contributor to mortality and morbidity worldwide and the most common cause of epilepsy in the elderly in high income nations. In recent years, it has become increasingly evident that both ischemic and hemorrhagic strokes induce dysfunction of the blood-brain barrier (BBB), and that this impairment can contribute to epileptogenesis. Nevertheless, studies directly comparing BBB dysfunction and poststroke epilepsy (PSE) are largely absent.
View Article and Find Full Text PDFElife
July 2024
Department of Brain and Cognitive Sciences, The School of Brain Sciences and Cognition, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Brain microvessels possess the unique properties of a blood-brain barrier (BBB), tightly regulating the passage of molecules from the blood to the brain neuropil and vice versa. In models of brain injury, BBB dysfunction and the associated leakage of serum albumin to the neuropil have been shown to induce pathological plasticity, neuronal hyper-excitability, and seizures. The effect of neuronal activity on BBB function and whether it plays a role in plasticity in the healthy brain remain unclear.
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