{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:55:51Z","timestamp":1774594551553,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,23]]},"group-title":"Pathology","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["P51OD011104-62 (X.Q.)"],"award-info":[{"award-number":["P51OD011104-62 (X.Q.)"]}]},{"name":"NIH","award":["R01DK129881 (X.Q)"],"award-info":[{"award-number":["R01DK129881 (X.Q)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  It remains unclear whether podocyte loss directly causes acute renal tubular cell (RTC) damage and interstitial fibrosis, thereby leading to renal failure. Here, we applied intermedilysin (ILY)-mediated human CD59 (hCD59) cell ablation to generate an acute, specific podocyte-ablation mouse model. Cre-induced hCD59 transgenics (ihCD59) were crossed with\n                  <jats:italic>Nphs2Cre<\/jats:italic>\n                  to generate\n                  <jats:italic>\n                    ihCD59\n                    <jats:sup>+\/-<\/jats:sup>\n                    \/Nphs2Cre\n                    <jats:sup>+\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice. The specific and rapid podocyte-ablation mediated by ILY injection directly caused RTC necrosis, leading to renal failure and even death within 2-3 days in a dose-dependent manner. Treating mice that received an ILY lethal dose with peritoneal dialysis or administering a non-lethal dose, we extended their survival beyond six weeks and found that mice developed interstitial fibrosis and glomerulosclerosis with persistent proteinuria and tubule damage. Podocyte-ablation caused massive disruption of glomerular function at week 1, and then partial recovery by week 2. Genes and pathways of TLRs and apoptosis, and mitochondrial functions were respectively upregulated and downregulated in both ablated-podocyte mouse and biopsied-glomerulonephritis patient kidney samples. Together, this rapid podocyte-ablation causes acute RTC necrosis that progresses to interstitial fibrosis in this mouse model, which is applicable for dissecting mechanisms underlying podocyte injury-mediated tubular damage and glomerular repair, with the potential to reveal novel therapeutic targets for kidney diseases.\n                <\/jats:p>","DOI":"10.64898\/2026.03.19.712955","type":"posted-content","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:24Z","timestamp":1774310424000},"source":"Crossref","is-referenced-by-count":0,"title":["Rapid Podocyte ablation Causes Acute Renal Tubule Cell Necrosis and Interstitial Fibrosis"],"prefix":"10.64898","author":[{"given":"Yilin","family":"Chen","sequence":"first","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Islamuddin","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jefferson","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avi","family":"Salomon","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella M","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shumei","family":"Liu","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecily C","family":"Midkiff","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryousuke","family":"Satou","sequence":"additional","affiliation":[{"name":"Department of Physiology and The Hypertension & Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia L.","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Physiology and The Hypertension & Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay K","family":"Kolls","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vecihi","family":"Batuman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Tulane University, New Orleans, LA, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhea","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Tulane University, New Orleans, LA, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert V","family":"Blair","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebin","family":"Qin","sequence":"additional","affiliation":[{"name":"Tulane National Biomedical Research Center, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026032622252068000_2026.03.19.712955v1.1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005010055"},{"key":"2026032622252068000_2026.03.19.712955v1.2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013050452"},{"key":"2026032622252068000_2026.03.19.712955v1.3","doi-asserted-by":"crossref","unstructured":"Watanabe M , Kakutani M , Nakano K , Okamura T , and Sasaki N . An inducible and podocyte-specific diphtheria toxin receptor knock-in mouse model for studying glomerular injury and chronic kidney disease progression. Febs j. 2025.","DOI":"10.1111\/febs.70333"},{"key":"2026032622252068000_2026.03.19.712955v1.4","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90519.2008"},{"key":"2026032622252068000_2026.03.19.712955v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.133"},{"key":"2026032622252068000_2026.03.19.712955v1.6","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012040414"},{"key":"2026032622252068000_2026.03.19.712955v1.7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010090963"},{"issue":"1","key":"2026032622252068000_2026.03.19.712955v1.8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/path.6370","article-title":"Podocyte YAP ablation decreases podocyte adhesion and exacerbates FSGS progression through \u03b13\u03b21 integrin","volume":"265","year":"2025","journal-title":"J Pathol"},{"key":"2026032622252068000_2026.03.19.712955v1.9","first-page":"226","article-title":"Genes and podocytes - new insights into mechanisms of podocytopathy","volume":"5","year":"2014","journal-title":"Front Endocrinol (Lausanne"},{"key":"2026032622252068000_2026.03.19.712955v1.10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112367"},{"key":"2026032622252068000_2026.03.19.712955v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.439"},{"issue":"2","key":"2026032622252068000_2026.03.19.712955v1.12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.gendis.2020.07.005","article-title":"Lipopolysaccharide-induced podocyte injury is regulated by calcineurin\/NFAT and TLR4\/MyD88\/NF-\u03baB signaling pathways through angiopoietin-like protein 4","volume":"9","year":"2022","journal-title":"Genes Dis"},{"issue":"1","key":"2026032622252068000_2026.03.19.712955v1.13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1159\/000479935","article-title":"New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL\/6 Mouse Strain","volume":"138","year":"2018","journal-title":"Nephron"},{"key":"2026032622252068000_2026.03.19.712955v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03243-w"},{"key":"2026032622252068000_2026.03.19.712955v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nm1674"},{"key":"2026032622252068000_2026.03.19.712955v1.16","doi-asserted-by":"publisher","DOI":"10.1172\/jci84921"},{"key":"2026032622252068000_2026.03.19.712955v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16158-z"},{"key":"2026032622252068000_2026.03.19.712955v1.18","doi-asserted-by":"crossref","unstructured":"Islamuddin M , Evangelista J , Kabir ME , Vidal AKN , Liu S , and Qin X . Rapid Depletion of Renal Macrophages using Human CD59\/Intermedilysin Cell Ablation Tool. J Vis Exp. 2025(219).","DOI":"10.3791\/67957"},{"key":"2026032622252068000_2026.03.19.712955v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10164"},{"issue":"2","key":"2026032622252068000_2026.03.19.712955v1.20","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.kint.2017.01.020","article-title":"Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury","volume":"92","year":"2017","journal-title":"Kidney Int"},{"key":"2026032622252068000_2026.03.19.712955v1.21","doi-asserted-by":"crossref","first-page":"1755141","DOI":"10.3389\/fimmu.2026.1755141","article-title":"Characterization of subchronic lung and brain consequences caused by mouse-adapted SARS-CoV-2 and influenza A infection of C57BL6 mice","volume":"17","year":"2026","journal-title":"Front Immunol"},{"key":"2026032622252068000_2026.03.19.712955v1.22","doi-asserted-by":"publisher","DOI":"10.2337\/db19-2301-PUB"},{"key":"2026032622252068000_2026.03.19.712955v1.23","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00037.2020"},{"key":"2026032622252068000_2026.03.19.712955v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17340"},{"key":"2026032622252068000_2026.03.19.712955v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.1.1"},{"key":"2026032622252068000_2026.03.19.712955v1.26","doi-asserted-by":"publisher","DOI":"10.1086\/302182"},{"key":"2026032622252068000_2026.03.19.712955v1.27","first-page":"S51","article-title":"Congenital nephrotic syndrome","volume":"53","year":"1996","journal-title":"Kidney Int Suppl"},{"issue":"3","key":"2026032622252068000_2026.03.19.712955v1.28","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1159\/000124236","article-title":"Podocyte Injury Induced by Albumin Overload in vivo and in vitro: Involvement of TGF-Beta and p38 MAPK","volume":"108","year":"2008","journal-title":"Nephron Experimental Nephrology"},{"key":"2026032622252068000_2026.03.19.712955v1.29","first-page":"1478697","article-title":"Tubulointerstitial injury in proteinuric chronic kidney diseases","volume":"11","year":"2024","journal-title":"Front Med (Lausanne"},{"key":"2026032622252068000_2026.03.19.712955v1.30","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3389\/fimmu.2019.00672","article-title":"Complement Therapeutics in Autoimmune Disease","volume":"10","year":"2019","journal-title":"Front Immunol"},{"issue":"15","key":"2026032622252068000_2026.03.19.712955v1.31","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1111\/jcmm.17451","article-title":"Aristolochic acid I induces proximal tubule injury through ROS\/HMGB1\/mt DNA mediated activation of TLRs","volume":"26","year":"2022","journal-title":"J Cell Mol Med"},{"key":"2026032622252068000_2026.03.19.712955v1.32","doi-asserted-by":"crossref","unstructured":"Upadhyay R , Ying WZ , Nasrin Z , Safah H , Jaimes EA , Feng W , et al. Free light chains injure proximal tubule cells through the STAT1\/HMGB1\/TLR axis. JCI Insight. 2020;5(14).","DOI":"10.1172\/jci.insight.137191"},{"key":"2026032622252068000_2026.03.19.712955v1.33","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070722"},{"key":"2026032622252068000_2026.03.19.712955v1.34","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007090982"},{"issue":"2","key":"2026032622252068000_2026.03.19.712955v1.35","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.3390\/ijms24021415","article-title":"Toll-like Receptor 4 in Acute Kidney Injury","volume":"24","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"2026032622252068000_2026.03.19.712955v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.11.024"},{"issue":"1","key":"2026032622252068000_2026.03.19.712955v1.37","doi-asserted-by":"crossref","first-page":"16182","DOI":"10.1038\/s41598-021-95504-7","article-title":"Deletion of TLR4 reduces apoptosis and improves histology in a murine kidney transplant model","volume":"11","year":"2021","journal-title":"Sci Rep"},{"issue":"4","key":"2026032622252068000_2026.03.19.712955v1.38","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s00467-019-04454-w","article-title":"Proteinuria-take a closer look!","volume":"35","year":"2020","journal-title":"Pediatr Nephrol."},{"issue":"12","key":"2026032622252068000_2026.03.19.712955v1.39","doi-asserted-by":"crossref","first-page":"e81703","DOI":"10.1371\/journal.pone.0081703","article-title":"Urinary immunoglobulin G to albumin ratio and N-Acetyl-Beta-D-Glucosaminidase as early predictors of therapeutic response in ANCA-associated glomerulonephritis","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"2026032622252068000_2026.03.19.712955v1.40","doi-asserted-by":"crossref","unstructured":"Comper WD , Vuchkova J , and McCarthy KJ . New insights into proteinuria\/albuminuria. Frontiers in Physiology. 2022;Volume 13 - 2022.","DOI":"10.3389\/fphys.2022.991756"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.19.712955","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:25:37Z","timestamp":1774589137000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.19.712955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":40,"URL":"https:\/\/doi.org\/10.64898\/2026.03.19.712955","relation":{},"subject":[],"published":{"date-parts":[[2026,3,23]]},"subtype":"preprint"}}