{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:05:51Z","timestamp":1758931551020,"version":"3.44.0"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Settlement Fund for the New Faculty of Konyang University Hospital"},{"name":"Konyang University Myunggok Research Fund"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Particulate matter (PM) exposure is linked to chronic kidney disease; however, its effect on immunoglobulin A (IgA) nephropathy (IgAN) remains unclear. We investigated whether PM exposure exacerbates IgAN in a mouse model. HIGA mice (IgAN model) and BALB\/c controls were exposed to PM in a sealed chamber for 13 weeks. Lung Toll-like receptor 9 (TLR9) expression, serum aberrantly glycosylated IgA, A proliferation-inducing ligand (APRIL) levels, mesangial IgA deposition, and kidney pathology were assessed. RNA sequencing of splenic B cells was performed to evaluate immune-related gene expression. PM exposure increased lung TLR9 expression in both strains, particularly around pigment-laden macrophages. HIGA mice showed elevated aberrant IgA and APRIL levels, with aggravated mesangial expansion and IgA deposition. Transcriptomic analysis revealed immune dysregulation in splenic B cells of PM-exposed HIGA mice. Our findings provide experimental evidence that PM exposure aggravates IgAN via TLR9-mediated mucosal immune activation, leading to aberrant IgA glycosylation and mesangial deposition. These findings emphasize that reducing PM exposure may benefit patients with IgAN.<\/jats:p>","DOI":"10.3390\/ijms26199387","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:31:28Z","timestamp":1758875488000},"page":"9387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Particulate Matter on the Exacerbation of Immunoglobulin A Nephropathy: An Animal Experimental Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-8106","authenticated-orcid":false,"given":"Minhyeok","family":"Lee","sequence":"first","affiliation":[{"name":"Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"},{"name":"Division of Pulmonology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daeun","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Woong","family":"Son","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan Jin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sin Yung","family":"Woo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4170-0762","authenticated-orcid":false,"given":"Mi Jin","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusin","family":"Pak","sequence":"additional","affiliation":[{"name":"Sensor System Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se-Hee","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Min","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Ro","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7416-1841","authenticated-orcid":false,"given":"Yohan","family":"Park","sequence":"additional","affiliation":[{"name":"Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"},{"name":"Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.envint.2014.10.005","article-title":"A review on the human health impact of airborne particulate matter","volume":"74","author":"Kim","year":"2015","journal-title":"Environ. Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Johnston, F.H., Bailie, R.S., Pilotto, L.S., and Hanigan, I.C. (2007). Ambient biomass smoke and cardio-respiratory hospital admissions in Darwin, Australia. BMC Public Health, 7.","DOI":"10.1186\/1471-2458-7-240"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1001\/jama.299.18.2172","article-title":"Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among Medicare patients","volume":"299","author":"Peng","year":"2008","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1681\/ASN.2017030253","article-title":"Particulate matter air pollution and the risk of incident CKD and progression to ESRD","volume":"29","author":"Bowe","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1289\/ehp.1510269","article-title":"Long-term exposure to ambient fine particulate matter and renal function in older men: The Veterans Administration normative aging study","volume":"124","author":"Mehta","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41370-021-00351-3","article-title":"The association between fine particulate matter (PM2.5) and chronic kidney disease using electronic health record data in urban Minnesota","volume":"32","author":"Ghazi","year":"2022","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.envint.2018.10.007","article-title":"Kidney damage induced by sub-chronic fine particulate matter exposure","volume":"121","author":"Mateos","year":"2018","journal-title":"Environ. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2403222","DOI":"10.1002\/advs.202403222","article-title":"Kidney injury evoked by fine particulate matter: Risk factor, causation, mechanism and intervention study","volume":"11","author":"Hou","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12989-016-0179-8","article-title":"Early kidney damage induced by subchronic exposure to PM2.5 in rats","volume":"13","author":"Barbier","year":"2016","journal-title":"Part. Fibre Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.kint.2022.08.020","article-title":"Particulate matter of air pollution may increase risk of kidney failure in IgA nephropathy","volume":"102","author":"Luo","year":"2022","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1681\/ASN.2016010093","article-title":"Long-term exposure to air pollution and increased risk of membranous nephropathy in China","volume":"27","author":"Xu","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1016\/j.ekir.2024.05.013","article-title":"Elevated exposure to air pollutants accelerates primary glomerular disease progression","volume":"9","author":"Troost","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41572-023-00476-9","article-title":"IgA nephropathy","volume":"9","author":"Stamellou","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1681\/ASN.2011050464","article-title":"The pathophysiology of IgA nephropathy","volume":"22","author":"Suzuki","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1056\/NEJMoa2305635","article-title":"A Phase 2 trial of Sibeprenlimab in patients with IgA nephropathy","volume":"390","author":"Mathur","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1056\/NEJMoa2410316","article-title":"Alternative complement pathway inhibition with iptacopan in IgA nephropathy","volume":"392","author":"Perkovic","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1056\/NEJMoa2409415","article-title":"Atrasentan in patients with IgA nephropathy","volume":"392","author":"Heerspink","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"452","DOI":"10.2215\/CJN.0000000000000384","article-title":"Phase 2 trial of Cemdisiran in adult patients with IgA nephropathy: A randomized controlled trial","volume":"19","author":"Barratt","year":"2024","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ekir.2022.12.014","article-title":"Randomized Phase 2 trial of Telitacicept in patients with IgA nephropathy with persistent proteinuria","volume":"8","author":"Lv","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.kint.2024.03.012","article-title":"A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy","volume":"105","author":"Lafayette","year":"2024","journal-title":"Kidney Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"452","DOI":"10.23876\/j.krcp.21.146","article-title":"A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy","volume":"41","author":"Han","year":"2022","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153007","DOI":"10.1016\/j.prp.2020.153007","article-title":"Tonsillar immunology in IgA nephropathy","volume":"216","author":"Yang","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gesualdo, L., Di Leo, V., and Coppo, R. (2021). The mucosal immune system and IgA nephropathy. Seminars in Immunopathology, Springer.","DOI":"10.1007\/s00281-021-00871-y"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Knoppova, B., Reily, C., King, R.G., Julian, B.A., Novak, J., and Green, T.J. (2021). Pathogenesis of IgA nephropathy: Current understanding and implications for development of disease-specific treatment. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194501"},{"key":"ref_25","first-page":"7506","article-title":"Function of PM2. 5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases","volume":"15","author":"Li","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1038\/ki.1996.517","article-title":"Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice","volume":"50","author":"Muso","year":"1996","journal-title":"Kidney Int."},{"key":"ref_27","unstructured":"Japan SLC, Inc (2025, September 23). HIGA\/NscSlc Experimental Animal Data Sheet, Hamamatsu, Japan, Available online: http:\/\/www.jslc.co.jp\/pdf\/data\/2007\/higa2007.pdf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.kint.2019.08.022","article-title":"TLR9 activation induces aberrant IgA glycosylation via APRIL- and IL-6-mediated pathways in IgA nephropathy","volume":"97","author":"Makita","year":"2020","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/1465-9921-12-149","article-title":"Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8+ T cells in chronic obstructive pulmonary disease","volume":"12","author":"Nadigel","year":"2011","journal-title":"Respir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"L154","DOI":"10.1152\/ajplung.00073.2016","article-title":"TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice","volume":"311","author":"Foronjy","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1681\/ASN.20233411S1243a","article-title":"Nucleotide-sensing TLR9\/TLR7 system is a potential therapeutic target for IgA nephropathy: TH-PO546","volume":"34","author":"Lee","year":"2023","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1681\/ASN.2007121303","article-title":"CD19+ CD5+ B cells in primary IgA nephropathy","volume":"19","author":"Yuling","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111209","DOI":"10.1016\/j.intimp.2023.111209","article-title":"Integrated analysis of ATAC-seq and RNA-seq unveils the role of ferroptosis in PM2. 5-induced asthma exacerbation","volume":"125","author":"Zhang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mar\u00edn-Palma, D., Fernandez, G.J., Ruiz-Saenz, J., Taborda, N.A., Rugeles, M.T., and Hernandez, J.C. (2023). Particulate matter impairs immune system function by up-regulating inflammatory pathways and decreasing pathogen response gene expression. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-39921-w"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"dvaf008","DOI":"10.1093\/eep\/dvaf008","article-title":"Exposure to fine particulate matter in adults is associated with immune cell gene expression related to inflammation, the electron transport chain, and cell cycle regulation","volume":"11","author":"Rundblad","year":"2025","journal-title":"Environ. Epigenet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1681\/ASN.2004030219","article-title":"Genome-wide scan in a novel IgA nephropathy model identifies a susceptibility locus on murine chromosome 10, in a region syntenic to human IGAN1 on chromosome 6q22\u201323","volume":"16","author":"Suzuki","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1681\/ASN.2011121160","article-title":"Development of a model of early-onset IgA nephropathy","volume":"23","author":"Okazaki","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kim, S.J., Koo, H.M., Lim, B.J., Oh, H.J., Yoo, D.E., Shin, D.H., Lee, M.J., Doh, F.M., Park, J.T., and Yoo, T.H. (2012). Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040495"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.coi.2005.04.005","article-title":"The role of APRIL and BAFF in lymphocyte activation","volume":"17","author":"Schneider","year":"2005","journal-title":"Curr. Opin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1172\/JCI0215034","article-title":"APRIL modulates B and T cell immunity","volume":"109","author":"Stein","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/bcpt.13915","article-title":"Comparison of acute phase response in mice after inhalation and intratracheal instillation of molybdenum disulphide and tungsten particles","volume":"133","author":"Gutierrez","year":"2023","journal-title":"Basic. Clin. Pharmacol. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ge, S.X., Son, E.W., and Yao, R. (2018). iDEP: An integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2486-6"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tang, D., Chen, M., Huang, X., Zhang, G., Zeng, L., Zhang, G., Wu, S., and Wang, Y. (2023). SRplot: A free online platform for data visualization and graphing. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0294236"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:32:26Z","timestamp":1758875546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199387"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199387","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]}}}