Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway

Albumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na<sup>+</sup> transport drives alveolar fluid clearance (AFC...

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Main Authors: Mandy Laube, Ulrich H. Thome
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/15/8823
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author Mandy Laube
Ulrich H. Thome
author_facet Mandy Laube
Ulrich H. Thome
author_sort Mandy Laube
collection DOAJ
description Albumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na<sup>+</sup> transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na<sup>+</sup> transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na<sup>+</sup> transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na<sup>+</sup> transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na<sup>+</sup> transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na<sup>+</sup> transport was caused by an increased maximal ENaC activity, while Na,K-ATPase activity remained unchanged. Acute and chronic BSA treatment lowered membrane permeability, confirming the increased barrier integrity observed in Ussing chambers. Western blots demonstrated an increased phosphorylation of AKT and SGK1, and PI3K inhibition abolished the stimulating effect of BSA. BSA therefore enhanced epithelial Na<sup>+</sup> transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway.
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spelling doaj.art-c86f2c02d1a34fa2be2e4dcd6e5ad8972023-11-30T22:31:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315882310.3390/ijms23158823Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 PathwayMandy Laube0Ulrich H. Thome1Center for Pediatric Research Leipzig, Division of Neonatology, Department of Pediatrics, University of Leipzig, 04103 Leipzig, GermanyCenter for Pediatric Research Leipzig, Division of Neonatology, Department of Pediatrics, University of Leipzig, 04103 Leipzig, GermanyAlbumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na<sup>+</sup> transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na<sup>+</sup> transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na<sup>+</sup> transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na<sup>+</sup> transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na<sup>+</sup> transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na<sup>+</sup> transport was caused by an increased maximal ENaC activity, while Na,K-ATPase activity remained unchanged. Acute and chronic BSA treatment lowered membrane permeability, confirming the increased barrier integrity observed in Ussing chambers. Western blots demonstrated an increased phosphorylation of AKT and SGK1, and PI3K inhibition abolished the stimulating effect of BSA. BSA therefore enhanced epithelial Na<sup>+</sup> transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway.https://www.mdpi.com/1422-0067/23/15/8823lungNa<sup>+</sup> transportbarrier integrityENaCBSAprotein kinase B
spellingShingle Mandy Laube
Ulrich H. Thome
Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway
International Journal of Molecular Sciences
lung
Na<sup>+</sup> transport
barrier integrity
ENaC
BSA
protein kinase B
title Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway
title_full Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway
title_fullStr Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway
title_full_unstemmed Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway
title_short Albumin Stimulates Epithelial Na<sup>+</sup> Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway
title_sort albumin stimulates epithelial na sup sup transport and barrier integrity by activating the pi3k akt sgk1 pathway
topic lung
Na<sup>+</sup> transport
barrier integrity
ENaC
BSA
protein kinase B
url https://www.mdpi.com/1422-0067/23/15/8823
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