{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:05:48Z","timestamp":1790381148575,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SNUBH Research Fund","award":["16-2018-0011"],"award-info":[{"award-number":["16-2018-0011"]}]},{"name":"SNUBH Research Fund","award":["2019R1A2C1085411"],"award-info":[{"award-number":["2019R1A2C1085411"]}]},{"name":"SNUBH Research Fund","award":["20008413"],"award-info":[{"award-number":["20008413"]}]},{"name":"National Research Foundation","award":["16-2018-0011"],"award-info":[{"award-number":["16-2018-0011"]}]},{"name":"National Research Foundation","award":["2019R1A2C1085411"],"award-info":[{"award-number":["2019R1A2C1085411"]}]},{"name":"National Research Foundation","award":["20008413"],"award-info":[{"award-number":["20008413"]}]},{"name":"Ministry of Trade, Industry and Energy (MOTIE), Korea","award":["16-2018-0011"],"award-info":[{"award-number":["16-2018-0011"]}]},{"name":"Ministry of Trade, Industry and Energy (MOTIE), Korea","award":["2019R1A2C1085411"],"award-info":[{"award-number":["2019R1A2C1085411"]}]},{"name":"Ministry of Trade, Industry and Energy (MOTIE), Korea","award":["20008413"],"award-info":[{"award-number":["20008413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.<\/jats:p>","DOI":"10.3390\/ijms25105121","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:27:11Z","timestamp":1715171231000},"page":"5121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis"],"prefix":"10.3390","volume":"25","author":[{"given":"Shin Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Yeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4225-0270","authenticated-orcid":false,"given":"Eun Jeong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungwan","family":"Seo","sequence":"additional","affiliation":[{"name":"Osong Medical Innovation Foundation, Cheongju-si 28161, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hyuk","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seokwoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Jun","family":"Chin","sequence":"additional","affiliation":[{"name":"Osong Medical Innovation Foundation, Cheongju-si 28161, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Young","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-9962","authenticated-orcid":false,"given":"Sejoong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"ref_1","first-page":"154","article-title":"The European renal association-European dialysis and transplant association registry annual report 2014: A summary","volume":"10","author":"Pippias","year":"2017","journal-title":"Clin. Kidney J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1083\/jcb.201410017","article-title":"Review series: The cell biology of renal filtration","volume":"209","author":"Scott","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.drudis.2015.06.003","article-title":"Targeting the podocyte to treat glomerular kidney disease","volume":"20","author":"Lal","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/157339908783502370","article-title":"Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy","volume":"4","author":"Ziyadeh","year":"2008","journal-title":"Curr. Diabetes Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-981-13-8871-2_10","article-title":"Role of Podocyte Injury in Glomerulosclerosis","volume":"1165","author":"Lu","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1159\/000507997","article-title":"Mechanisms of Podocyte Detachment, Podocyturia, and Risk of Progression of Glomerulopathies","volume":"6","author":"Trimarchi","year":"2020","journal-title":"Kidney Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/environments1010014","article-title":"Review of Evidence of Environmental Impacts of Animal Research and Testing","volume":"1","author":"Groff","year":"2014","journal-title":"Environments"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?","volume":"4","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1021\/acscentsci.9b01097","article-title":"h-FIBER: Microfluidic Topographical Hollow Fiber for Studies of Glomerular Filtration Barrier","volume":"6","author":"Xie","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Roye, Y., Bhattacharya, R., Mou, X., Zhou, Y., Burt, M.A., and Musah, S. (2021). A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium. Micromachines, 12.","DOI":"10.3390\/mi12080967"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, S.Y., and Mahler, G.J. (2021). Modelling Renal Filtration and Reabsorption Processes in a Human Glomerulus and Proximal Tubule Microphysiological System. Micromachines, 12.","DOI":"10.22541\/au.161762817.75993814\/v1"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"\u2018t Hart, D.C., Yildiz, D., Palacio-Casta\u00f1eda, V., Li, L., Gumuscu, B., Brock, R., Verdurmen, W., van der Vlag, J., and Nijenhuis, T. (2023). Co-Culture of Glomerular Endothelial Cells and Podocytes in a Custom-Designed Glomerulus-on-a-Chip Model Improves the Filtration Barrier Integrity and Affects the Glomerular Cell Phenotype. Biosensors, 13.","DOI":"10.3390\/bios13030339"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kwon, E.J., Choi, Y., Kim, S.Y., Park, S., Yun, G., Min, S.H., and Kim, S. (2024). Development of Drug Efficacy Testing Platform for Glomerulonephritis. Micromachines, 15.","DOI":"10.3390\/mi15030317"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31771","DOI":"10.1038\/srep31771","article-title":"Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy","volume":"6","author":"Zhou","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1038\/s41467-019-11577-z","article-title":"A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier","volume":"10","author":"Petrosyan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/ndt\/gfh633","article-title":"Histological grading of IgA nephropathy predicting renal outcome: Revisiting H. S. Lee\u2019s glomerular grading system","volume":"20","author":"Lee","year":"2005","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1681\/ASN.V133630","article-title":"A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression","volume":"13","author":"Saleem","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0092-8674(03)00120-X","article-title":"Cellular motility driven by assembly and disassembly of actin filaments","volume":"112","author":"Pollard","year":"2003","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1681\/ASN.2013070795","article-title":"Glomerular Cell Cross-Talk Influences Composition and Assembly of Extracellular Matrix","volume":"25","author":"Byron","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.kint.2016.09.044","article-title":"Characterization of Glomerular Extracellular Matrix by Proteomic Analysis of Laser-Captured Microdissected Glomeruli","volume":"91","author":"Hobeika","year":"2017","journal-title":"Kidney Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"481520","DOI":"10.1155\/2012\/481520","article-title":"Mechanisms of glomerular albumin filtration and tubular reabsorption","volume":"2012","author":"Tojo","year":"2012","journal-title":"Int. J. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrneph.2013.109","article-title":"The glomerular basement membrane as a barrier to albumin","volume":"9","author":"Suh","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1681\/ASN.2010090963","article-title":"Podocyte injury damages other podocytes","volume":"22","author":"Matsusaka","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.kint.2016.01.012","article-title":"Podocyte injury and its consequences","volume":"89","author":"Nagata","year":"2016","journal-title":"Kidney Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"F660","DOI":"10.1152\/ajprenal.00234.2011","article-title":"Marker expression, behaviors, and responses vary in different lines of conditionally immortalized cultured podocytes","volume":"301","author":"Chittiprol","year":"2011","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_26","first-page":"1481","article-title":"Crocin protects podocytes against oxidative stress and inflammation induced by high glucose through inhibition of NF-\u03baB. Cell","volume":"42","author":"Li","year":"2017","journal-title":"Physiol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.2337\/diabetes.54.6.1626","article-title":"From the periphery of the glomerular capillary wall toward the center of disease: Podocyte injury comes of age in diabetic nephropathy","volume":"54","author":"Wolf","year":"2005","journal-title":"Diabetes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nm1731","article-title":"The Notch pathway in podocytes plays a role in the development of glomerular disease","volume":"14","author":"Niranjan","year":"2008","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/ndt\/gfaa211","article-title":"Novel in vitro assays to detect circulating permeability factor(s) in idiopathic focal segmental glomerulosclerosis","volume":"36","author":"Maas","year":"2021","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1242\/dev.119.4.1329","article-title":"Nuclear localization of the protein encoded by the Wilms\u2019 tumor gene WT1 in embryonic and adult tissues","volume":"119","author":"Mundlos","year":"1993","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1084-9521(03)00026-0","article-title":"WT1 and glomerular function","volume":"14","author":"Menke","year":"2003","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/path.1390","article-title":"The WT1-heterozygous mouse: A model to study the development of glomerular sclerosis","volume":"200","author":"Menke","year":"2003","journal-title":"J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2353\/ajpath.2006.050398","article-title":"Pathophysiologic implications of reduced podocyte number in a rat model of progressive glomerular injury","volume":"168","author":"Macconi","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_34","first-page":"519","article-title":"Experimental model of focal sclerosis. I. Relationship to protein excretion in aminonucleoside nephrosis","volume":"36","author":"Glasser","year":"1977","journal-title":"Lab. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1440-1797.2010.01383.x","article-title":"Adriamycin nephropathy: A model of focal segmental glomerulosclerosis","volume":"16","author":"Lee","year":"2011","journal-title":"Nephrology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1159\/000337175","article-title":"Tacrolimus improves the proteinuria remission in patients with refractory IgA nephropathy","volume":"35","author":"Zhang","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Peng, L., Ma, J., Cui, R., Chen, X., Wei, S.Y., Wei, Q.J., and Li, B. (2014). The calcineurin inhibitor tacrolimus reduces proteinuria in membranous nephropathy accompanied by a decrease in angiopoietin-like-4. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106164"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2147\/IJNRD.S344725","article-title":"Glomerulus-on-a-Chip: Current Insights and Future Potential Towards Recapitulating Selectively Permeable Filtration Systems","volume":"15","author":"Doi","year":"2022","journal-title":"Int. J. Nephrol. Renovasc. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1681\/ASN.2007111244","article-title":"Induction of T regulatory cells attenuates idiopathic nephrotic syndrome","volume":"20","author":"Bruneau","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1007\/s00467-009-1214-x","article-title":"T regulatory cell function in idiopathic minimal lesion nephrotic syndrome","volume":"24","author":"Araya","year":"2009","journal-title":"Pediatr. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1097\/01.ASN.0000016406.82019.B3","article-title":"T cells and minimal change disease","volume":"13","author":"Cunard","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1681\/ASN.2007040395","article-title":"TLR4 links podocytes with the innate immune system to mediate glomerular injury","volume":"19","author":"Banas","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/art.20103","article-title":"Is alpha-actinin a target for pathogenic anti-DNA antibodies in lupus nephritis?","volume":"50","author":"Mason","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1681\/ASN.2008050549","article-title":"The mesangial cell revisited: No cell is an island","volume":"20","author":"Schlondorff","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1208\/s12248-018-0248-z","article-title":"Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules","volume":"20","author":"Vormann","year":"2018","journal-title":"AAPS J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/2211068214561025","article-title":"TEER measurement techniques for in vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J. Lab. Autom."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1083\/jcb.201704045","article-title":"FiloQuant reveals increased filopodia density during breast cancer progression","volume":"216","author":"Jacquemet","year":"2017","journal-title":"J. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5121\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:41:58Z","timestamp":1760107318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105121"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105121","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]}}}