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Albumin Stimulates Epithelial Na+ 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+ transport drives alveolar fluid clearance (AFC), enabling air breathi...
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Published in: | International journal of molecular sciences 2022-08, Vol.23 (15), p.8823 |
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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+ transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na+ transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na+ transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na+ transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na+ transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na+ 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+ transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway. |
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It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na+ transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na+ transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na+ transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na+ transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na+ transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na+ 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+ transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23158823</identifier><identifier>PMID: 35955955</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Albumin ; Albumins ; Alveoli ; barrier integrity ; BSA ; Cell culture ; Chambers ; Chronic effects ; Edema ; ENaC ; Fetuses ; Gene expression ; Kinases ; lung ; Membrane permeability ; Na+ transport ; Na+/K+-exchanging ATPase ; Osmosis ; Osmotic pressure ; Permeability ; Phosphorylation ; Physiology ; Premature babies ; Premature birth ; protein kinase B ; Proteins ; Respiratory distress syndrome ; Serum proteins ; Western blotting</subject><ispartof>International journal of molecular sciences, 2022-08, Vol.23 (15), p.8823</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na+ transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na+ transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na+ transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na+ transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na+ transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na+ 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+ transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Albumin</subject><subject>Albumins</subject><subject>Alveoli</subject><subject>barrier integrity</subject><subject>BSA</subject><subject>Cell culture</subject><subject>Chambers</subject><subject>Chronic effects</subject><subject>Edema</subject><subject>ENaC</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Kinases</subject><subject>lung</subject><subject>Membrane permeability</subject><subject>Na+ transport</subject><subject>Na+/K+-exchanging ATPase</subject><subject>Osmosis</subject><subject>Osmotic pressure</subject><subject>Permeability</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Premature babies</subject><subject>Premature birth</subject><subject>protein kinase B</subject><subject>Proteins</subject><subject>Respiratory distress syndrome</subject><subject>Serum proteins</subject><subject>Western blotting</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkl1rFDEUhgdRbK3e-QMC3gi6bj4mmeRGWEutyxYtdL0OZ_Kxm2VmsiaZyv57Z90irRBIOHnOw8vhVNVbgj8xpvA87PpMGeFSUvasOic1pTOMRfP80fusepXzDmPKKFcvqzPGFT-e8yosunbsw4DuSujHDorL6GofytZ1ATr0HT6gdYIh72MqCAaLvkBKwSW0HIrbpFAOqD2ghSnhHkoYNmjqRLdLtpovVuv53fWKoFso299weF298NBl9-bhvqh-fr1aX36b3fy4Xl4ubmam5rzMTMs5Z4LU0hMhZOucrFvWSAqsJl4Z5aVvlCHeklrwlkJNuBcCE0eJtI1kF9Xy5LURdnqfQg_poCME_bcQ00ZDKsF0ThspPDWYWjLJPdDWUVdbY4XjYKVqJtfnk2s_tr2zxg0lQfdE-vRnCFu9ifdaMSEVPYZ5_yBI8dfoctF9yMZ1HQwujlnTBk-xBWvEhL77D93FMQ3TqI4UbjgjEk_UxxNlUsw5Of8vDMH6uA_68T6wP3HPpn8</recordid><startdate>20220801</startdate><enddate>20220801</enddate><creator>Laube, Mandy</creator><creator>Thome, Ulrich H.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7180-2858</orcidid></search><sort><creationdate>20220801</creationdate><title>Albumin Stimulates Epithelial Na+ Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway</title><author>Laube, Mandy ; Thome, Ulrich H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-cb55536148f1668bee84b3782a341f9c9f8f79c1fd1465b2a415f6601e218d783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Albumin</topic><topic>Albumins</topic><topic>Alveoli</topic><topic>barrier integrity</topic><topic>BSA</topic><topic>Cell culture</topic><topic>Chambers</topic><topic>Chronic effects</topic><topic>Edema</topic><topic>ENaC</topic><topic>Fetuses</topic><topic>Gene expression</topic><topic>Kinases</topic><topic>lung</topic><topic>Membrane permeability</topic><topic>Na+ transport</topic><topic>Na+/K+-exchanging ATPase</topic><topic>Osmosis</topic><topic>Osmotic pressure</topic><topic>Permeability</topic><topic>Phosphorylation</topic><topic>Physiology</topic><topic>Premature babies</topic><topic>Premature birth</topic><topic>protein kinase B</topic><topic>Proteins</topic><topic>Respiratory distress syndrome</topic><topic>Serum proteins</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laube, Mandy</creatorcontrib><creatorcontrib>Thome, Ulrich H.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laube, Mandy</au><au>Thome, Ulrich H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Albumin Stimulates Epithelial Na+ Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway</atitle><jtitle>International journal of molecular sciences</jtitle><date>2022-08-01</date><risdate>2022</risdate><volume>23</volume><issue>15</issue><spage>8823</spage><pages>8823-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Albumin is a major serum protein and is frequently used as a cell culture supplement. 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subjects | 1-Phosphatidylinositol 3-kinase AKT protein Albumin Albumins Alveoli barrier integrity BSA Cell culture Chambers Chronic effects Edema ENaC Fetuses Gene expression Kinases lung Membrane permeability Na+ transport Na+/K+-exchanging ATPase Osmosis Osmotic pressure Permeability Phosphorylation Physiology Premature babies Premature birth protein kinase B Proteins Respiratory distress syndrome Serum proteins Western blotting |
title | Albumin Stimulates Epithelial Na+ Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway |
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