Unveiling the Role of Calcium Dobesilate's based on Multi-omics in Combatting Type 1 Diabetic Nephropathy

Unveiling the Role of Calcium Dobesilate's based on Multi-omics in Combatting Type 1 Diabetic Nephropathy | 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 Unveiling the Role of Calcium Dobesilate's based on Multi-omics in Combatting Type 1 Diabetic Nephropathy zhang li, Tong Yin, Xiang Liu, Xiaoying Dong, Ping Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9122473/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: Diabetic nephropathy seriously endangers patients' lives and imposes a heavy economic burden on the country. Its molecular mechanism and therapeutic targets are not yet fully understood. A deeper understanding of the molecular mechanism of diabetic nephropathy is conducive to slowing down the disease progression and developing new strategies to reduce the risk of end-stage renal disease. Calcium dobesilate (CaD) has a vascular protective effect, but its systemic mechanism in type 1 diabetic nephropathy (T1DKD) has not yet been studied through multi-omics integration. Methods: We conducted transcriptomic, proteomic, and metabolomic profiling, using renal tissues obtained from rats from three groups (NC: non-diabetic; T1DKD: type-1 diabetic kidney disease; AS: CaD-treated T1DKD). Differential expression analysis, pathway enrichment (GO/KEGG/Reactome), and multi-omics integration (nine-quadrant plots, hierarchical clustering, correlation networks) were employed to dissect disease mechanisms and drug effects. Results: Transcriptomics identified 2,301 differentially expressed genes (DEGs) in T1DKD vs NC, enriched in extracellular matrix organization and ECM–receptor interaction, and cell adhesion (NES = -1.841, P <0.01). 214 DEGs were identified in AS vs T1DKD, enriched in immune-inflammatory pathways, activation of the renin-angiotensin system, and extracellular space (NES=1.681, P <0.01). CaD reversed 73 DEGs, involved in tryptophan metabolism and steroid biosynthesis. Proteomics validated 154 Differentially abundant proteins (DAPs) in T1DKD vs NC, linked to immune response activation and RAS hyperactivity, while CaD modulated 14 DAPs involved in innate immune system regulation. CaD reversed 2 DAPs involved in the upregulation of P2RX7 protein. Metabolomics highlighted Pyrimidine metabolism and Vitamin B6 metabolism. Nine-quadrant analysis revealed CaD-driven restoration of steroid biosynthesis ( Cyp27b1 ) and tryptophan metabolism ( Aadat , Cat ). P2RX7 emerged as a calcium signaling hub, negatively correlating with Taurine. Conclusion: Our study delineates systemic molecular disruptions in T1DKD and establishes CaD as a multi-target therapeutic agent that restores metabolic homeostasis and mitigates renal injury through coordinated regulation of tryptophan, and steroid pathway. These findings provide a mechanistic foundation for repurposing CaD in T1DKD management. Type-1 diabetic nephropathy Calcium dobesilate Transcriptome Proteome Metabolome 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. 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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-9122473","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":610165870,"identity":"f415fba3-6b6e-49bc-bb1e-8aa2d4d561d6","order_by":0,"name":"zhang li","email":"","orcid":"","institution":"General Hospital of Ningxia medical university","correspondingAuthor":false,"prefix":"","firstName":"zhang","middleName":"","lastName":"li","suffix":""},{"id":610165871,"identity":"549bc75b-9cd3-4ee3-8933-4818425f2fce","order_by":1,"name":"Tong Yin","email":"","orcid":"","institution":"General Hospital of Ningxia medical university","correspondingAuthor":false,"prefix":"","firstName":"Tong","middleName":"","lastName":"Yin","suffix":""},{"id":610165872,"identity":"25f3c05d-9532-4de9-96e7-a6513440dd3d","order_by":2,"name":"Xiang Liu","email":"","orcid":"","institution":"General Hospital of Ningxia medical university","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Liu","suffix":""},{"id":610165873,"identity":"3daf9802-1484-4ff5-8b17-40e273caf188","order_by":3,"name":"Xiaoying Dong","email":"","orcid":"","institution":"General Hospital of Ningxia medical university","correspondingAuthor":false,"prefix":"","firstName":"Xiaoying","middleName":"","lastName":"Dong","suffix":""},{"id":610165874,"identity":"772a50f1-6bdb-42d6-b5d6-3ef70fa8a0bf","order_by":4,"name":"Ping Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYBACAwj1v56fmbH5wQcDGztitTAnSLY3HzOcUZCWTLwWgzPHEqR5PhxibCCkxZz97LEHH/ew5THcyDEwtjE4wMzAfvjoBnxaLHvy0g1nPOMpZpyRY/A4x+AOHwNPWtoNvA47kGMmzXNAgrFZAmhLjsEzZgYJHjP8Ws6/MZP+c8CAsQ2oRdrC4DBjA0EtN4C2MBxISOzhAXqfgTgtb8wkew4cMJZgBwZyj0FaMhtBv5zPMZP4ceCAnP1hYFT++GNjx89++BheLZiAjTTlo2AUjIJRMAqwAQARh00T8mm0pQAAAABJRU5ErkJggg==","orcid":"","institution":"General Hospital of Ningxia medical university","correspondingAuthor":true,"prefix":"","firstName":"Ping","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2026-03-14 12:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9122473/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9122473/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107482873,"identity":"b630ca98-b5ba-4e90-807c-df6b3226b7f8","added_by":"auto","created_at":"2026-04-22 02:25:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":758576,"visible":true,"origin":"","legend":"","description":"","filename":"UnveilingtheRoleofCalciumDobesilatesbasedonMultiomicsinCombattingType1DiabeticNephropathy.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9122473/v1_covered_f6c7afbc-8877-4ffb-8fc3-7f202a23d974.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unveiling the Role of Calcium Dobesilate's based on Multi-omics in Combatting Type 1 Diabetic Nephropathy","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":"Type-1 diabetic nephropathy, Calcium dobesilate, Transcriptome, Proteome, Metabolome","lastPublishedDoi":"10.21203/rs.3.rs-9122473/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9122473/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Diabetic nephropathy seriously endangers patients' lives and imposes a heavy economic burden on the country. Its molecular mechanism and therapeutic targets are not yet fully understood. A deeper understanding of the molecular mechanism of diabetic nephropathy is conducive to slowing down the disease progression and developing new strategies to reduce the risk of end-stage renal disease. Calcium dobesilate (CaD) has a vascular protective effect, but its systemic mechanism in type 1 diabetic nephropathy (T1DKD) has not yet been studied through multi-omics integration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted transcriptomic, proteomic, and metabolomic profiling, using renal tissues obtained from rats from three groups (NC: non-diabetic; T1DKD: type-1 diabetic kidney disease; AS: CaD-treated T1DKD). Differential expression analysis, pathway enrichment (GO/KEGG/Reactome), and multi-omics integration (nine-quadrant plots, hierarchical clustering, correlation networks) were employed to dissect disease mechanisms and drug effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eTranscriptomics identified 2,301 differentially expressed genes (DEGs) in T1DKD vs NC, enriched in extracellular matrix organization and ECM–receptor interaction, and cell adhesion (NES = -1.841, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.01). 214 DEGs were identified in AS vs T1DKD, enriched in immune-inflammatory pathways, activation of the renin-angiotensin system, and extracellular space (NES=1.681, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.01). CaD reversed 73 DEGs, involved in tryptophan metabolism and steroid biosynthesis. Proteomics validated 154 Differentially abundant proteins (DAPs) in T1DKD vs NC, linked to immune response activation and RAS hyperactivity, while CaD modulated 14 DAPs involved in innate immune system regulation. CaD reversed 2 DAPs involved in the upregulation of P2RX7 protein. Metabolomics highlighted Pyrimidine metabolism and Vitamin B6 metabolism. Nine-quadrant analysis revealed CaD-driven restoration of steroid biosynthesis (\u003cem\u003eCyp27b1\u003c/em\u003e) and tryptophan metabolism (\u003cem\u003eAadat\u003c/em\u003e, \u003cem\u003eCat\u003c/em\u003e). P2RX7 emerged as a calcium signaling hub, negatively correlating with Taurine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003eOur study delineates systemic molecular disruptions in T1DKD and establishes CaD as a multi-target therapeutic agent that restores metabolic homeostasis and mitigates renal injury through coordinated regulation of tryptophan, and steroid pathway. These findings provide a mechanistic foundation for repurposing CaD in T1DKD management.\u003c/p\u003e","manuscriptTitle":"Unveiling the Role of Calcium Dobesilate's based on Multi-omics in Combatting Type 1 Diabetic Nephropathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-25 06:24:15","doi":"10.21203/rs.3.rs-9122473/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":"d8fd5560-9fc7-414d-a495-1bbb4b918a5b","owner":[],"postedDate":"March 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-19T09:54:33+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-25 06:24:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9122473","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9122473","identity":"rs-9122473","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}