Asprosin Promotes High Glucose-Induced Apoptosis of Human Renal Tubular Epithelial Cells by Inhibiting Autophagy

Asprosin Promotes High Glucose-Induced Apoptosis of Human Renal Tubular Epithelial Cells by Inhibiting Autophagy | 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 Asprosin Promotes High Glucose-Induced Apoptosis of Human Renal Tubular Epithelial Cells by Inhibiting Autophagy Shuran Zheng, Wenli Liu, Xiaogang Du This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7243474/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 Asprosin, a recently discovered adipokine, is a glucotropic hormone involved in the pathogenesis of diabetes and closely associated with diabetic kidney disease (DKD). Renal tubular epithelial cell injury is one of the important pathological characteristics of DKD. However, the precise molecular mechanism remains unclear. In this study, we aimed to investigate the role of Asprosin in proximal tubular epithelial cells injury in DKD. Methods The plasma Asprosin level was measured using ELISA in both healthy people and patients with DKD. Immunohistochemistry was employed to detect the level of Asprosin in renal biopsy tissues from DKD patients as well as normal renal tissues adjacent to cancer resected by surgery. Western Blot and q-PCR were utilized to determine the level of Asprosin in DKD mouse kidney tissues. HK-2 cells were exposed to high glucose conditions to simulate injury in renal tubular epithelial cells seen in DKD patients. Following intervention with Asprosin, we analyzed the expression of HK-2 gene, autophagic flux and apoptosis. Results The expression level of Asprosin was found to be higher in kidney tissues and plasma from DKD patients compared to the control group. In addition, the kidney tissues of DKD mice and HK-2 cells treated with high glucose exhibited elevated levels of Asprosin expression. Furthermore, intervention with Asprosin in HK-2 cells resulted in insufficient autophagy and increased apoptosis. These findings suggest that Asprosin exacerbates disturbance in autophagy and induces apoptosis in HK-2 cells under the high glucose conditions. Importantly, our results indicate that Asprosin promotes the apoptosis of HK-2 cells by inhibiting autophagy. Conclusions Our findings collectively demonstrate that elevated glucose levels can induce the upregulation of Asprosin in both kidney tissue and plasma. Furthermore, Asprosin has the ability to enhance apoptosis in HK-2 cells by inhibiting autophagy, exacerbate autophagy dysregulation and apoptosis caused by high glucose, as well as promote injury in renal tubular epithelial cells. Asprosin Autophagy Apoptosis HK-2 Diabetic Kidney Disease 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. 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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-7243474","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":505523567,"identity":"2d94fed5-7371-46a5-849e-7c05f46bea53","order_by":0,"name":"Shuran Zheng","email":"","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shuran","middleName":"","lastName":"Zheng","suffix":""},{"id":505523568,"identity":"c2f17acf-6d22-4ec1-b115-282285803843","order_by":1,"name":"Wenli Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenli","middleName":"","lastName":"Liu","suffix":""},{"id":505523569,"identity":"da52308e-72c6-4d94-b883-0a2b1ee366ec","order_by":2,"name":"Xiaogang Du","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArUlEQVRIiWNgGAWjYDCCA2DShoefv4E0LWkykjMOkKblsI1BQwKROvhupF/8zJtznseA4QDjh485RGiRPHOmWHLmtts85swNzEAGEVoMjvekMXwEarFsOMDGzEuUlsM8aQyJ287xGBxIIFbL8fZjQFsOkKAF6BeQF5J5JGccbCbOL8AQe/iZd5udPT9/88EPH4nRwsAADF4IYGwgSj0QsD8gVuUoGAWjYBSMVAAAtMk5S2WqMZwAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiaogang","middleName":"","lastName":"Du","suffix":""}],"badges":[],"createdAt":"2025-07-29 12:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7243474/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7243474/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95654159,"identity":"a7c744f2-8e9f-4d3f-ba57-955d97949c18","added_by":"auto","created_at":"2025-11-11 16:10:05","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1245367,"visible":true,"origin":"","legend":"","description":"","filename":"AsprosinPromotesHighGlucoseInducedApoptosisofHumanRenalTubularEpithelialCellsbyInhibitingAutophagy.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7243474/v1_covered_433860ff-2a6b-420a-9e7a-b2be77ca4d9c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Asprosin Promotes High Glucose-Induced Apoptosis of Human Renal Tubular Epithelial Cells by Inhibiting Autophagy","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":"Asprosin, Autophagy, Apoptosis, HK-2, Diabetic Kidney Disease","lastPublishedDoi":"10.21203/rs.3.rs-7243474/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7243474/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAsprosin, a recently discovered adipokine, is a glucotropic hormone involved in the pathogenesis of diabetes and closely associated with diabetic kidney disease (DKD). Renal tubular epithelial cell injury is one of the important pathological characteristics of DKD. However, the precise molecular mechanism remains unclear. In this study, we aimed to investigate the role of Asprosin in proximal tubular epithelial cells injury in DKD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe plasma Asprosin level was measured using ELISA in both healthy people and patients with DKD. Immunohistochemistry was employed to detect the level of Asprosin in renal biopsy tissues from DKD patients as well as normal renal tissues adjacent to cancer resected by surgery. Western Blot and q-PCR were utilized to determine the level of Asprosin in DKD mouse kidney tissues. HK-2 cells were exposed to high glucose conditions to simulate injury in renal tubular epithelial cells seen in DKD patients. Following intervention with Asprosin, we analyzed the expression of HK-2 gene, autophagic flux and apoptosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe expression level of Asprosin was found to be higher in kidney tissues and plasma from DKD patients compared to the control group. In addition, the kidney tissues of DKD mice and HK-2 cells treated with high glucose exhibited elevated levels of Asprosin expression. Furthermore, intervention with Asprosin in HK-2 cells resulted in insufficient autophagy and increased apoptosis. These findings suggest that Asprosin exacerbates disturbance in autophagy and induces apoptosis in HK-2 cells under the high glucose conditions. Importantly, our results indicate that Asprosin promotes the apoptosis of HK-2 cells by inhibiting autophagy.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eOur findings collectively demonstrate that elevated glucose levels can induce the upregulation of Asprosin in both kidney tissue and plasma. Furthermore, Asprosin has the ability to enhance apoptosis in HK-2 cells by inhibiting autophagy, exacerbate autophagy dysregulation and apoptosis caused by high glucose, as well as promote injury in renal tubular epithelial cells.\u003c/p\u003e","manuscriptTitle":"Asprosin Promotes High Glucose-Induced Apoptosis of Human Renal Tubular Epithelial Cells by Inhibiting Autophagy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 17:29:48","doi":"10.21203/rs.3.rs-7243474/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":"b1c99585-dcc1-47a4-9c55-f0cbebedb4b5","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T10:27:54+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-27 17:29:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7243474","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7243474","identity":"rs-7243474","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}