Drosha in mesangial cells regulates Glomerular Capillary Tufts Formation Through Drosha/Ribosome/Gata3 Axis

Drosha in mesangial cells regulates Glomerular Capillary Tufts Formation Through Drosha/Ribosome/Gata3 Axis | 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 Drosha in mesangial cells regulates Glomerular Capillary Tufts Formation Through Drosha/Ribosome/Gata3 Axis Jin Tang, Lang Qin, Jiajia Qin, Zixuan Fan, Tingxuan Xu, Wenjun Xiao, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8257080/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 5 You are reading this latest preprint version Abstract Drosha is a critical regulator of kidney development; its loss or mutation, identified in a subsets of Wilms tumor (WT), a pediatric kidney cancer, leads to nephric cap mesenchyme developmental defects. Here, we investigated the role of Drosha in mesangial cells and its impact on glomerular capillary tuft formation. Mesangial cells specific deletion of Drosha (Drosha cKO) in mouse model was generated. Deletion of Drosha in mesangial cells disrupted the glomerular capillary tufts formation, leading to dysplastic glomeruli, proteinuria, oliguria, reduced looping of glomerular capillaries and capillary dilation. Drosha knockdown in mesangial cells (SV40 MES 13) leads to decreased cell proliferation and reduced Gata3 protein level. Transcriptome analysis by RNA-seq shows decreased levels of ribosomal protein genes (RPGs) but unaltered mRNA levels of major genes affecting kidney development, including Gata3, Pax2, Atn1, Wt1 etc. in Drosha-KD compared to Control SV40 MES13 cells. Further analysis indicates Drosha regulates the translation of Gata3 in mesangial cells via regulating RPG transcription. Removal of Drosha in adult mesangial cells did not cause significant kidney dysfunction, indicating that Drosha functions primarily during development rather than in homeostasis. Our work reveals that Drosha in mesangial cells orchestrates the formation of glomerular capillary tufts by regulating Gata3 translation. It identifies the critical role of DROSHA in nephric development and proposes DROSHA as a novel potential causal gene for congenital anomalies of the kidney and the urinary tract (CAKUT). Pericytes Mesangial cells Kidney development Drosha Ribosomal protein Full Text Supplementary Files SupplementaryTable1Listofprimersequences.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Major Revision 18 Jan, 2026 Reviewers agreed at journal 04 Dec, 2025 Reviewers invited by journal 04 Dec, 2025 Editor assigned by journal 03 Dec, 2025 First submitted to journal 01 Dec, 2025 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-8257080","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":555486323,"identity":"149ac778-21bb-4a25-abf7-81b99a83f38f","order_by":0,"name":"Jin Tang","email":"","orcid":"","institution":"Sun Yat-Sen University","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Tang","suffix":""},{"id":555486324,"identity":"2854146b-1a0e-4e63-a72b-25c95665c6e5","order_by":1,"name":"Lang Qin","email":"","orcid":"","institution":"Sun Yat-Sen 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