{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:35:51Z","timestamp":1751430951874,"version":"3.41.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700579"],"award-info":[{"award-number":["81700579"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"13th Five-Year Key Plan for the Military Medical Scientific Research Project","award":["CBJ14L016"],"award-info":[{"award-number":["CBJ14L016"]}]},{"name":"The Hebei Province Health Planning Committee Project","award":["20230258"],"award-info":[{"award-number":["20230258"]}]},{"name":"Shenzhen Science and Technology Development Fundamental Research Project","award":["JCYJ20220530164802006"],"award-info":[{"award-number":["JCYJ20220530164802006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and hypothesis<\/jats:title>\n                  <jats:p>The levels of C5b-9, terminal products of complement activation, were significantly elevated in autosomal dominant polycystic kidney disease (ADPKD). However, the precise mechanisms by which C5b-9 facilitates cyst growth remain incompletely elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Three groups of chronic-onset Pkd1\u2212\/\u2212 mice were established: one group received intravenous injections of 0.5\u00a0mg\/kg C5b-9, another was administered 1.0\u00a0mg\/kg monoclonal anti-C9 antibodies, and a control group received 1\u00a0mg\/kg IgG isotype control. All treatments were administered biweekly for two months (postnatal day 180\u2013240). Renal macrophages from distinct subsets were sorted using fluorescence-activated cell sorting. To deplete macrophages, liposome clodronate was injected intraperitoneally. Sublethal irradiation followed by bone marrow reconstruction was performed in Pkd1\u2212\/\u2212 mice to evaluate the role of bone marrow-derived macrophages (BMDMs) in ADPKD progression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>(i) In vitro, sublytic C5b-9 did not affect the viability of renal tubular epithelial cells, but significantly induced M1-like polarization and pyroptosis of BMDMs. (ii) In vivo, C5b-9 notably triggered pyroptosis of Ly6C+ monocytes and a reduction in circulating monocyte numbers as cysts enlarged. (iii) Residual Ly6C+ monocytes infiltrated renal tissues and differentiated into Ly6C+ macrophages, which exhibited a greater susceptibility to pyroptosis compared to Ly6C\u2212 macrophages. (iv) Although limited evidence has recently suggested that Ly6C\u2212 monocytes may also be affected by C5b-9, upregulation of CCR2 in Ly6C\u2212 macrophages was observed in C5b-9-treated Pkd1\u2212\/\u2212 mice, implying that Ly6C\u2212 monocytes could represent a significant source of M2 macrophages.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>C5b-9 infusion promoted renal tubular epithelial cell proliferation by inducing pyroptosis of Ly6C+ monocytes\/macrophages, contributing to progressive cyst enlargement in chronic-onset PKD mice.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfae262","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:40:12Z","timestamp":1731372012000},"page":"1161-1174","source":"Crossref","is-referenced-by-count":1,"title":["Monocyte\/macrophage pyroptosis and C5b-9-induced cyst enlargement in Pkd1\u2212\/\u2212 mice"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4347-0064","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"The 981th Hospital of Chinese People's Liberation Army Department of Nephrology, , Chengde ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyang","family":"Kong","sequence":"additional","affiliation":[{"name":"Shenzhen Bao'An District Song Gang People's Hospital Department of Nephrology, , Shenzhen ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihan","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Tenth People's Hospital, TongJi University Department of Nephrology, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Lv","sequence":"additional","affiliation":[{"name":"Chang Zheng Hospital, the Navy Military Medical University Kidney Institution of the Chinese People's Liberation Army, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2818-6620","authenticated-orcid":false,"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Affiliated Shuguang Hospital, Shanghai University of Traditional Chinese Medicine Department of Nephrology, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-9406","authenticated-orcid":false,"given":"Cheng","family":"Xue","sequence":"additional","affiliation":[{"name":"Chang Zheng Hospital, the Navy Military Medical University Kidney Institution of the Chinese People's Liberation Army, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuwei","family":"Song","sequence":"additional","affiliation":[{"name":"Chang Zheng Hospital, the Navy Military Medical University Kidney Institution of the Chinese People's Liberation Army, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Song","sequence":"additional","affiliation":[{"name":"Hainan Hospital of General Hospital of Chinese People's Liberation Army Clinical Laboratory, , Sanya ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Ma","sequence":"additional","affiliation":[{"name":"Beidaihe Rehabilitation and Recuperation Center of the Chinese People's Liberation Army Kidney Diagnostic and Therapeutic Center of People's Liberation Army, , Qinhuangdao ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiguo","family":"Mao","sequence":"additional","affiliation":[{"name":"Chang Zheng Hospital, the Navy Military Medical University Kidney Institution of the Chinese People's Liberation Army, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changlin","family":"Mei","sequence":"additional","affiliation":[{"name":"Chang Zheng Hospital, the Navy Military Medical University Kidney Institution of the Chinese People's Liberation Army, , Shanghai ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"2025053005074333800_bib1","doi-asserted-by":"publisher","first-page":"iv15","DOI":"10.1093\/ndt\/gfu017","article-title":"Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival\u2014an analysis of data from the ERA-EDTA Registry","volume":"29","author":"Spithoven","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"2025053005074333800_bib2","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1681\/ASN.2018010074","article-title":"Interactions between macrophages and cyst-lining epithelial cells promote kidney cyst growth in Pkd1-deficient mice","volume":"29","author":"Yang","year":"2018","journal-title":"JASN"},{"key":"2025053005074333800_bib3","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3389\/fimmu.2020.00734","article-title":"Inflammaging and complement system: a link between acute kidney injury and chronic graft damage","volume":"11","author":"Franzin","year":"2020","journal-title":"Front Immunol"},{"key":"2025053005074333800_bib4","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.1681\/ASN.2015090994","article-title":"Proteomics of urinary vesicles links plakins and complement to polycystic kidney disease","volume":"27","author":"Salih","year":"2016","journal-title":"JASN"},{"key":"2025053005074333800_bib5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1559-0275-9-13","article-title":"Urine proteome of autosomal dominant polycystic kidney disease patients","volume":"9","author":"Bakun","year":"2012","journal-title":"Clin Proteom"},{"key":"2025053005074333800_bib6","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/joim.12214","article-title":"Excessive activation of the alternative complement pathway in autosomal dominant polycystic kidney disease","volume":"276","author":"Su","year":"2014","journal-title":"J Intern Med"},{"key":"2025053005074333800_bib7","doi-asserted-by":"publisher","first-page":"F584","DOI":"10.1152\/ajprenal.00176.2019","article-title":"Diagnostic roles of urinary kidney injury molecule 1 and soluble C5b-9 in acute tubulointerstitial nephritis","volume":"317","author":"Zhao","year":"2019","journal-title":"Am J Physiol Renal Physiol"},{"key":"2025053005074333800_bib8","doi-asserted-by":"publisher","first-page":"877988","DOI":"10.3389\/fphar.2022.877988","article-title":"Membrane attack complex C5b-9 promotes renal tubular epithelial cell pyroptosis in trichloroethylene-sensitized mice","volume":"13","author":"Wang","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025053005074333800_bib9","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.semnephrol.2013.08.009","article-title":"Complement-mediated cellular injury","volume":"33","author":"Takano","year":"2013","journal-title":"Semin Nephrol"},{"key":"2025053005074333800_bib10","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/ki.2008.659","article-title":"Inactivation of Pkd1 in principal cells causes a more severe cystic kidney disease than in intercalated cells","volume":"75","author":"Raphael","year":"2009","journal-title":"Kidney Int"},{"key":"2025053005074333800_bib11","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","article-title":"Necroptosis, pyroptosis and apoptosis: an intricate game of cell death","volume":"18","author":"Bertheloot","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"2025053005074333800_bib12","doi-asserted-by":"publisher","first-page":"8643","DOI":"10.1038\/s41598-017-07889-z","article-title":"Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy","volume":"7","author":"Liu","year":"2017","journal-title":"Sci Rep"},{"key":"2025053005074333800_bib13","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: an overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2025053005074333800_bib14","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.3389\/fimmu.2018.02563","article-title":"Inflammasome-independent role of NLRP3 mediates mitochondrial regulation in renal injury","volume":"9","author":"Kim","year":"2018","journal-title":"Front Immunol"},{"key":"2025053005074333800_bib15","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1080\/15548627.2022.2084862","article-title":"Mitochondria ROS and mitophagy in acute kidney injury","volume":"19","author":"Su","year":"2023","journal-title":"Autophagy"},{"key":"2025053005074333800_bib16","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1194\/jlr.M072587","article-title":"NLRP3 inflammasome as a novel target for docosahexaenoic acid metabolites to abrogate glomerular injury","volume":"58","author":"Li","year":"2017","journal-title":"J Lipid Res"},{"key":"2025053005074333800_bib17","doi-asserted-by":"publisher","first-page":"C355","DOI":"10.1152\/ajpcell.00403.2020","article-title":"Long noncoding RNA Kcnq1ot1 promotes sC5b-9-induced podocyte pyroptosis by inhibiting miR-486a-3p and upregulating NLRP3","volume":"320","author":"Zhang","year":"2021","journal-title":"Am J Physiol Cell Physiol"},{"key":"2025053005074333800_bib18","doi-asserted-by":"publisher","first-page":"bvaa029","DOI":"10.1210\/jendso\/bvaa029","article-title":"The role of podocytes and podocyte-associated biomarkers in diagnosis and treatment of diabetic kidney disease","volume":"4","author":"Kravets","year":"2020","journal-title":"J Endocr Soc"},{"key":"2025053005074333800_bib19","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1007\/s10753-023-01806-5","article-title":"Dehydration accelerates cytogenesis and cyst growth in Pkd1(-\/-) mice by regulating macrophage M2 polarization","volume":"46","author":"Yang","year":"2023","journal-title":"Inflammation"},{"key":"2025053005074333800_bib20","doi-asserted-by":"publisher","first-page":"176460","DOI":"10.1016\/j.ejphar.2024.176460","article-title":"Demotion of canonical\/non-canonical inflammasome and pyroptosis alleviates ischemia\/reperfusion-induced acute kidney injury: novel role of the D2\/D3 receptor agonist ropinirole","volume":"969","author":"Henedak","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"2025053005074333800_bib21","doi-asserted-by":"publisher","first-page":"e926254","DOI":"10.12659\/MSM.926254","article-title":"The protein kinase R inhibitor C16 alleviates sepsis-induced acute kidney injury through modulation of the NF-\u03baB and NLR family pyrin domain-containing 3 (NLPR3) pyroptosis signal pathways","volume":"26","author":"Zhou","year":"2020","journal-title":"Med Sci Monit"},{"key":"2025053005074333800_bib22","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41420-022-00894-w","article-title":"Myoglobin promotes macrophage polarization to M1 type and pyroptosis via the RIG-I\/Caspase1\/GSDMD signaling pathway in CS-AKI","volume":"8","author":"Li","year":"2022","journal-title":"Cell Death Discov"},{"key":"2025053005074333800_bib23","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/jcpe.13258","article-title":"NLRP3 inflammasome mediates M1 macrophage polarization and IL-1\u03b2 production in inflammatory root resorption","volume":"47","author":"Zhang","year":"2020","journal-title":"J Clinic Periodontology"},{"key":"2025053005074333800_bib24","doi-asserted-by":"publisher","first-page":"795048","DOI":"10.3389\/fimmu.2021.795048","article-title":"The cGAS-STING pathway: a promising immunotherapy target","volume":"12","author":"Ou","year":"2021","journal-title":"Front Immunol"},{"key":"2025053005074333800_bib25","doi-asserted-by":"publisher","first-page":"e1008335","DOI":"10.1371\/journal.ppat.1008335","article-title":"STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection","volume":"16","author":"Wang","year":"2020","journal-title":"PLoS Pathog"},{"key":"2025053005074333800_bib26","doi-asserted-by":"publisher","first-page":"F1284","DOI":"10.1152\/ajprenal.00428.2015","article-title":"The C-terminal tail of polycystin-1 regulates complement factor B expression by signal transducer and activator of transcription 1","volume":"310","author":"Wu","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"2025053005074333800_bib27","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.7150\/ijbs.69652","article-title":"Sublytic C5b-9 induces CCL3\/4 production and macrophage accumulation in Thy-1\u00a0N rats via PKC-\u03b1\/p65\/IRF-8 axis","volume":"18","author":"Wang","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2025053005074333800_bib28","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.kint.2020.09.033","article-title":"Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis","volume":"99","author":"Boudhabhay","year":"2021","journal-title":"Kidney Int"},{"key":"2025053005074333800_bib29","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.1681\/ASN.2014070714","article-title":"Cause of death in patients with reduced kidney function","volume":"26","author":"Thompson","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2025053005074333800_bib30","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.2337\/db14-0256","article-title":"Mannose-binding lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity","volume":"63","author":"Stienstra","year":"2014","journal-title":"Diabetes"},{"key":"2025053005074333800_bib31","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/eji.201948227","article-title":"The role of the complement factor B-arginase-polyamine molecular axis in uremia-induced cardiac remodeling in mice","volume":"50","author":"Yang","year":"2020","journal-title":"Eur J Immunol"},{"key":"2025053005074333800_bib32","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1681\/ASN.2013080864","article-title":"Scattered deletion of PKD1 in kidneys causes a cystic snowball effect and recapitulates polycystic kidney disease","volume":"26","author":"Leonhard","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2025053005074333800_bib33","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12929-015-0151-1","article-title":"Complement and macrophage crosstalk during process of angiogenesis in tumor progression","volume":"22","author":"Khan","year":"2015","journal-title":"J Biomed Sci"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfae262\/60597664\/gfae262.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/40\/6\/1161\/60597664\/gfae262.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/40\/6\/1161\/60597664\/gfae262.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T09:07:46Z","timestamp":1748596066000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/40\/6\/1161\/7890819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,11,11]]},"published-print":{"date-parts":[[2025,5,30]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfae262","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"type":"print","value":"0931-0509"},{"type":"electronic","value":"1460-2385"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2024,11,11]]}}}