The Integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in Alcohol induced ARDS

The Integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in Alcohol induced ARDS | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in Alcohol induced ARDS xue dai, xueling liu, meijun liu, ting li, daoxin wang, wang deng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9227947/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Acute respiratory distress syndrome (ARDS) is characterized by impaired alveolar-capillary permeability and pulmonary edema. Alveolar fluid clearance (AFC) is strongly associated with patient prognosis. Objective This study aimed to investigate whether chronic alcohol consumption affects sodium channel regulation in ARDS via the Integrin αvβ6/TGF-β1/Smad4 signaling pathway. Methods We established chronic alcohol exposure models in mice and MLE-12 cells, followed by lipopolysaccharide (LPS)-induced ARDS in both systems. The Integrin αvβ6/TGF-β1/Smad4 pathway was inhibited to explore its regulatory effect on ENaC and Na⁺,K⁺-ATPase during alcohol-induced ARDS. Results We found that chronic alcohol consumption exacerbated lung injury by activating this signaling pathway, which suppressed ENaC and Na⁺,K⁺-ATPase protein expression. Inhibition of the pathway alleviated pulmonary edema and inflammation and improved survival rates. Both in vivo and in vitro results demonstrated that the Integrin αvβ6/TGF-β1/Smad4 pathway regulates ENaC and Na⁺,K⁺-ATPase in alcohol-induced ARDS. Conclusions These findings may clarify the regulatory mechanisms of sodium channels in ARDS associated with chronic alcohol consumption. Chronic alcohol abuse Acute respiratory distress syndrome Alveolar Fluid Clearance Epithelial Sodium Channel Sodium-potassium pump Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9227947","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":619538979,"identity":"7488c819-885f-4bfd-aeb0-84036381906c","order_by":0,"name":"xue dai","email":"","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"xue","middleName":"","lastName":"dai","suffix":""},{"id":619538980,"identity":"af8c9fed-9aa3-473e-ae5b-e95c4a0ea6ea","order_by":1,"name":"xueling liu","email":"","orcid":"","institution":"Second Affiliated Hospital of Chongqing Medical 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ARDS","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chronic alcohol abuse, Acute respiratory distress syndrome, Alveolar Fluid Clearance, Epithelial Sodium Channel, Sodium-potassium pump","lastPublishedDoi":"10.21203/rs.3.rs-9227947/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9227947/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute respiratory distress syndrome (ARDS) is characterized by impaired alveolar-capillary permeability and pulmonary edema. Alveolar fluid clearance (AFC) is strongly associated with patient prognosis.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to investigate whether chronic alcohol consumption affects sodium channel regulation in ARDS via the Integrin αvβ6/TGF-β1/Smad4 signaling pathway.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe established chronic alcohol exposure models in mice and MLE-12 cells, followed by lipopolysaccharide (LPS)-induced ARDS in both systems. The Integrin αvβ6/TGF-β1/Smad4 pathway was inhibited to explore its regulatory effect on ENaC and Na⁺,K⁺-ATPase during alcohol-induced ARDS.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe found that chronic alcohol consumption exacerbated lung injury by activating this signaling pathway, which suppressed ENaC and Na⁺,K⁺-ATPase protein expression. Inhibition of the pathway alleviated pulmonary edema and inflammation and improved survival rates. Both in vivo and in vitro results demonstrated that the Integrin αvβ6/TGF-β1/Smad4 pathway regulates ENaC and Na⁺,K⁺-ATPase in alcohol-induced ARDS.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThese findings may clarify the regulatory mechanisms of sodium channels in ARDS associated with chronic alcohol consumption.\u003c/p\u003e","manuscriptTitle":"The Integrin αvβ6/TGF-β1/Smad4 signaling pathway regulates ENaC in Alcohol induced ARDS","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 23:28:25","doi":"10.21203/rs.3.rs-9227947/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4af029a8-142b-493f-a540-e6e8665b0cae","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T17:39:51+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 23:28:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9227947","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9227947","identity":"rs-9227947","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}