Contrasting Effects of Endogenous and extracellular PCSK9 on Inflammation, Lipid alteration and Cell death.

Contrasting Effects of Endogenous and extracellular PCSK9 on Inflammation, Lipid alteration and Cell death. | 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 Article Contrasting Effects of Endogenous and extracellular PCSK9 on Inflammation, Lipid alteration and Cell death. Aram Ghalali, Fahd Alhamdan, Swapna Upadhyay, Koustav Ganguly, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3938453/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Aug, 2024 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the major regulators of low-density lipoprotein receptor (LDLR). While information on role and regulation of PCSK9 in lung is very limited, recent discovery of PCSK9 in A549 highlights a potential function of PCSK9 in lung. Our study focuses on understanding the role and regulation of PCSK9 in the lung. Experiments involved measurement of PCSK9 in bronchioalveolar lavage fluid (BALF), single cell sequencing analysis, and exposure of lung epithelial cells to PCSK9, cigarette smoke extract (CSE), and staurosporine. Inhibition of endogenous PCSK9 expression was followed by bulk RNA sequencing. PCSK9 levels were higher in BALF of smokers with or without chronic obstructive pulmonary diseases (COPD) compared to BALF of nonsmokers. PCSK9-stimulated cells induced proinflammatory cytokines and activation of MAPKp38. PCSK9 transcripts were highly expressed in healthy individuals compared to COPD, pulmonary fibrosis or pulmonary systemic sclerosis. CSE reduced PCSK9 levels in undifferentiated PBEC but induced in differentiated PBEC. PCSK9 inhibition affected biological pathways, inducing lipid peroxidation, and higher level of apoptosis in response to staurosporine. Our results suggest that higher levels of PCSK9 in BALF acts as an inflammatory marker. Furthermore, extracellular and endogenous PCSK9 play different roles. Health sciences/Medical research/Translational research Biological sciences/Cell biology PCSK9 lipid peroxidation PBEC BALF Apoptosis Fibrosis COPD PSS Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 13 Aug, 2024 Read the published version in Communications Biology → 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. 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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-3938453","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":273200125,"identity":"fa53cdd1-a25a-4474-ba2f-b0beec058456","order_by":0,"name":"Aram Ghalali","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Aram","middleName":"","lastName":"Ghalali","suffix":""},{"id":273200126,"identity":"e6dc6f29-cad8-4839-966f-66bc92be0aec","order_by":1,"name":"Fahd 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While information on role and regulation of PCSK9 in lung is very limited, recent discovery of PCSK9 in A549 highlights a potential function of PCSK9 in lung. Our study focuses on understanding the role and regulation of PCSK9 in the lung. Experiments involved measurement of PCSK9 in bronchioalveolar lavage fluid (BALF), single cell sequencing analysis, and exposure of lung epithelial cells to PCSK9, cigarette smoke extract (CSE), and staurosporine. Inhibition of endogenous PCSK9 expression was followed by bulk RNA sequencing. PCSK9 levels were higher in BALF of smokers with or without chronic obstructive pulmonary diseases (COPD) compared to BALF of nonsmokers. PCSK9-stimulated cells induced proinflammatory cytokines and activation of MAPKp38. PCSK9 transcripts were highly expressed in healthy individuals compared to COPD, pulmonary fibrosis or pulmonary systemic sclerosis. CSE reduced PCSK9 levels in undifferentiated PBEC but induced in differentiated PBEC. 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