{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:36:04Z","timestamp":1790368564242,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cadmium (Cd) is an environmental toxin that induces nephrotoxicity. Complement factor H (CFH), an inhibitor of complement activation, is involved in the pathogenesis of various renal diseases. In this study, we investigated the effects of Cd on CFH production by the kidney. In C57B6\/J mice, an increased CFH level was found in renal blood and glomerular endothelial cells after Cd treatment. In vitro, Cd induces an increased CFH secretion and mRNA expression in human renal glomerular endothelial cells but not in human podocytes or human mesangial cells. Cd activates the JNK pathway and increases c-Jun and c-Fos in human renal glomerular endothelial cells. A JNK inhibitor, SP600125, specifically abolishes Cd-induced CFH production. By chromatin immunoprecipitation assay and EMSA, the \u22121635 AP-1 motif on human CFH promoter was identified as the binding element for c-Jun and c-Fos. In a luciferase activity assay, mutation of the AP1 site eliminates Cd-induced increase of CFH promoter activity. Thus, the \u22121635 AP-1 motif on the CFH promoter region mediates Cd-inducible CFH gene expression.<\/jats:p>","DOI":"10.4049\/jimmunol.1800081","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T19:46:00Z","timestamp":1547495160000},"page":"1210-1218","source":"Crossref","is-referenced-by-count":18,"title":["Cadmium Induces Glomerular Endothelial Cell\u2013Specific Expression of Complement Factor H via the \u22121635 AP-1 Binding Site"],"prefix":"10.1093","volume":"202","author":[{"given":"Xiaocui","family":"Chen","sequence":"first","affiliation":[{"name":"Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University , Jinan, Shandong 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University , Jinan, Shandong 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University , Jinan, Shandong 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Hoh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-8214","authenticated-orcid":false,"given":"Carolyn M","family":"Kapron","sequence":"additional","affiliation":[{"name":"Department of Biology, Trent University , Peterborough, Ontario K9L 0G2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9932-2613","authenticated-orcid":false,"given":"Ju","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University , Jinan, Shandong 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,15]]},"reference":[{"key":"2025030417560658800_r1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s10534-010-9288-2","article-title":"Early biomarkers of cadmium exposure and nephrotoxicity","volume":"23","author":"Prozialeck","year":"2010","journal-title":"Biometals"},{"key":"2025030417560658800_r2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s10534-010-9328-y","article-title":"Heavy metal poisoning: the effects of cadmium on the kidney","volume":"23","author":"Johri","year":"2010","journal-title":"Biometals"},{"key":"2025030417560658800_r3","doi-asserted-by":"crossref","first-page":"p87","DOI":"10.1159\/000070241","article-title":"Nephrotoxicity and the proximal tubule. Insights from cadmium","volume":"93","author":"Th\u00e9venod","year":"2003","journal-title":"Nephron Physiol."},{"key":"2025030417560658800_r4","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.pharmthera.2007.01.001","article-title":"Cell adhesion molecules in chemically-induced renal injury","volume":"114","author":"Prozialeck","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"2025030417560658800_r5","doi-asserted-by":"crossref","first-page":"749010","DOI":"10.1155\/2012\/749010","article-title":"The glomerular filtration barrier: components and crosstalk","volume":"2012","author":"Menon","year":"2012","journal-title":"Int. J. Nephrol."},{"key":"2025030417560658800_r6","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s00467-011-1785-1","article-title":"Glomerular basement membrane composition and the filtration barrier","volume":"26","author":"Miner","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"2025030417560658800_r7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/jat.3168","article-title":"Short-term, low-dose cadmium exposure induces hyperpermeability in human renal glomerular endothelial cells","volume":"36","author":"Li","year":"2016","journal-title":"J. Appl. Toxicol."},{"key":"2025030417560658800_r8","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.lfs.2006.05.007","article-title":"The vascular endothelium as a target of cadmium toxicity","volume":"79","author":"Prozialeck","year":"2006","journal-title":"Life Sci."},{"key":"2025030417560658800_r9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3892\/ijmm.2016.2640","article-title":"NF-\u03baB signaling maintains the survival of cadmium-exposed human renal glomerular endothelial cells","volume":"38","author":"Zhang","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"2025030417560658800_r10","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrneph.2016.70","article-title":"Complement in disease: a defence system turning offensive","volume":"12","author":"Ricklin","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"2025030417560658800_r11","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025030417560658800_r12","doi-asserted-by":"crossref","first-page":"I9","DOI":"10.1016\/j.vaccine.2008.11.021","article-title":"Complement factor H related proteins in immune diseases","volume":"26","author":"Skerka","year":"2008","journal-title":"Vaccine"},{"key":"2025030417560658800_r13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molimm.2004.02.005","article-title":"The human complement factor H: functional roles, genetic variations and disease associations","volume":"41","author":"Rodr\u00edguez de C\u00f3rdoba","year":"2004","journal-title":"Mol. Immunol."},{"key":"2025030417560658800_r14","first-page":"83","article-title":"Complement receptors and related complement control proteins","volume":"51","author":"Sim","year":"1986","journal-title":"Biochem. Soc. Symp."},{"key":"2025030417560658800_r15","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00417-009-1049-y","article-title":"Regulated secretion of complement factor H by RPE and its role in RPE migration","volume":"247","author":"Kim","year":"2009","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"2025030417560658800_r16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.molimm.2008.10.029","article-title":"Human complement factor H-related protein 4 binds and recruits native pentameric C-reactive protein to necrotic cells","volume":"46","author":"Mihlan","year":"2009","journal-title":"Mol. Immunol."},{"key":"2025030417560658800_r17","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.7150\/jca.19452","article-title":"Loss of complement factor H in plasma increases endothelial cell migration","volume":"8","author":"Liu","year":"2017","journal-title":"J. Cancer"},{"key":"2025030417560658800_r18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.semnephrol.2013.08.002","article-title":"Dense deposit disease and C3 glomerulopathy","volume":"33","author":"Barbour","year":"2013","journal-title":"Semin. Nephrol."},{"key":"2025030417560658800_r19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.molimm.2015.03.012","article-title":"The role of complement in C3 glomerulopathy","volume":"67","author":"Zipfel","year":"2015","journal-title":"Mol. Immunol."},{"key":"2025030417560658800_r20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000445127","article-title":"Comprehensive analysis of complement genes in patients with atypical hemolytic uremic syndrome","volume":"43","author":"Zhang","year":"2016","journal-title":"Am. J. Nephrol."},{"key":"2025030417560658800_r21","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1681\/ASN.2005010078","article-title":"Membranoproliferative glomerulonephritis type II (dense deposit disease): an update","volume":"16","author":"Appel","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"2025030417560658800_r22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/nrneph.2014.217","article-title":"Histopathology of MPGN and C3 glomerulopathies","volume":"11","author":"Cook","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"2025030417560658800_r23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/ki.2011.115","article-title":"Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injury","volume":"80","author":"Renner","year":"2011","journal-title":"Kidney Int."},{"key":"2025030417560658800_r24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ajpath.2014.08.026","article-title":"Expression of human complement factor H prevents age-related macular degeneration-like retina damage and kidney abnormalities in aged Cfh knockout mice","volume":"185","author":"Ding","year":"2015","journal-title":"Am. J. Pathol."},{"key":"2025030417560658800_r25","doi-asserted-by":"crossref","first-page":"e0121994","DOI":"10.1371\/journal.pone.0121994","article-title":"Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies","volume":"10","author":"Turner","year":"2015","journal-title":"PLoS One"},{"key":"2025030417560658800_r26","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1161\/01.RES.0000255691.76142.4a","article-title":"Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms","volume":"100","author":"Aird","year":"2007","journal-title":"Circ. Res."},{"key":"2025030417560658800_r27","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.4049\/jimmunol.144.10.3835","article-title":"Differential regulation of complement factor H and C3 production in human umbilical vein endothelial cells by IFN-gamma and IL-1","volume":"144","author":"Brooimans","year":"1990","journal-title":"J. Immunol."},{"key":"2025030417560658800_r28","first-page":"E1693","article-title":"Loss of HtrA1-induced attenuation of TGF-\u03b2 signaling in fibroblasts might not be the main mechanism of CARASIL pathogenesis","volume":"112","author":"Liu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030417560658800_r29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0014-5793(96)00905-2","article-title":"Analysis of the recognition mechanism of the alternative pathway of complement by monoclonal anti-factor H antibodies: evidence for multiple interactions between H and surface bound C3b","volume":"393","author":"Jokiranta","year":"1996","journal-title":"FEBS Lett."},{"key":"2025030417560658800_r30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0167-5699(98)01432-7","article-title":"FHL-1\/reconectin: a human complement and immune regulator with cell-adhesive function","volume":"20","author":"Zipfel","year":"1999","journal-title":"Immunol. Today"},{"key":"2025030417560658800_r31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1172\/JCI86418","article-title":"VEGF regulates local inhibitory complement proteins in the eye and kidney","volume":"127","author":"Keir","year":"2017","journal-title":"J. Clin. Invest."},{"key":"2025030417560658800_r32","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.1182\/blood-2009-05-220434","article-title":"Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo","volume":"114","author":"Jin","year":"2009","journal-title":"Blood"},{"key":"2025030417560658800_r33","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1182\/blood-2010-06-287987","article-title":"Vascular bed-specific regulation of the von Willebrand factor promoter in the heart and skeletal muscle","volume":"117","author":"Liu","year":"2011","journal-title":"Blood"},{"key":"2025030417560658800_r34","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1182\/blood.V94.5.1673","article-title":"Induction of decay-accelerating factor by cytokines or the membrane-attack complex protects vascular endothelial cells against complement deposition","volume":"94","author":"Mason","year":"1999","journal-title":"Blood"},{"key":"2025030417560658800_r35","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1007\/s00204-013-1110-9","article-title":"Cadmium and cellular signaling cascades: interactions between cell death and survival pathways","volume":"87","author":"Th\u00e9venod","year":"2013","journal-title":"Arch. Toxicol."},{"key":"2025030417560658800_r36","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0955-0674(97)80068-3","article-title":"AP-1 function and regulation","volume":"9","author":"Karin","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"2025030417560658800_r37","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1136\/oemed-2014-102279","article-title":"Low-level cadmium exposure and effects on kidney function. [Published erratum appears in 2015 Occup. Environ. Med. 72: 898.]","volume":"71","author":"Wallin","year":"2014","journal-title":"Occup. Environ. Med."},{"key":"2025030417560658800_r38","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.envpol.2016.07.073","article-title":"Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia","volume":"218","author":"Zhang","year":"2016","journal-title":"Environ. Pollut."},{"key":"2025030417560658800_r39","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/nm902","article-title":"Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland","volume":"9","author":"Johnson","year":"2003","journal-title":"Nat. Med."},{"key":"2025030417560658800_r40","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/ki.2015.233","article-title":"An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy","volume":"88","author":"Nichols","year":"2015","journal-title":"Kidney Int."},{"key":"2025030417560658800_r41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrneph.2016.99","article-title":"Anti-complement-factor H-associated glomerulopathies","volume":"12","author":"Durey","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"2025030417560658800_r42","doi-asserted-by":"crossref","first-page":"44944","DOI":"10.18632\/oncotarget.16572","article-title":"Dose dependent effects of cadmium on tumor angiogenesis","volume":"8","author":"Wei","year":"2017","journal-title":"Oncotarget"},{"key":"2025030417560658800_r43","first-page":"207","article-title":"The vascular system as a target of metal toxicity","volume-title":"Toxicol. Sci.","author":"Prozialeck","year":"2008"},{"key":"2025030417560658800_r44","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.bbrc.2014.05.140","article-title":"Cadmium induces vascular permeability via activation of the p38 MAPK pathway","volume":"450","author":"Dong","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025030417560658800_r45","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.toxlet.2018.03.020","article-title":"Low dose cadmium upregulates the expression of von Willebrand factor in endothelial cells","volume":"290","author":"Wang","year":"2018","journal-title":"Toxicol. Lett."},{"key":"2025030417560658800_r46","doi-asserted-by":"crossref","first-page":"E990","DOI":"10.3390\/ijerph13100990","article-title":"Low dose cadmium inhibits proliferation of human renal mesangial cells via activation of the JNK pathway","volume":"13","author":"Chen","year":"2016","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"2025030417560658800_r47","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1006\/excr.2001.5180","article-title":"c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells","volume":"265","author":"Minet","year":"2001","journal-title":"Exp. Cell Res."},{"key":"2025030417560658800_r48","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.molimm.2011.08.013","article-title":"c-Jun and c-Fos regulate the complement factor H promoter in murine astrocytes","volume":"49","author":"Fraczek","year":"2011","journal-title":"Mol. Immunol."},{"key":"2025030417560658800_r49","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.humimm.2013.05.005","article-title":"Complement factor H gene (CFH) polymorphisms C-257T, G257A and haplotypes are associated with protection against severe dengue phenotype, possible related with high CFH expression","volume":"74","author":"Pastor","year":"2013","journal-title":"Hum. Immunol."},{"key":"2025030417560658800_r50","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.redox.2015.11.011","article-title":"Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: implications for age-related macular degeneration","volume":"7","author":"Marazita","year":"2016","journal-title":"Redox Biol."},{"key":"2025030417560658800_r51","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1111\/j.1538-7836.2005.01328.x","article-title":"Spatial and temporal dynamics of the endothelium","volume":"3","author":"Aird","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"2025030417560658800_r52","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF00224715","article-title":"Phenotypic heterogeneity of vascular endothelial cells in the human kidney","volume":"256","author":"Kinjo","year":"1989","journal-title":"Cell Tissue Res."},{"key":"2025030417560658800_r53","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.semnephrol.2012.02.001","article-title":"Vascular heterogeneity in the kidney","volume":"32","author":"Molema","year":"2012","journal-title":"Semin. Nephrol."},{"key":"2025030417560658800_r54","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.3892\/mmr.2015.3172","article-title":"Interleukin-1\u03b2 increases permeability and upregulates the expression of vascular endothelial-cadherin in human renal glomerular endothelial cells","volume":"11","author":"Du","year":"2015","journal-title":"Mol. Med. Rep."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/202\/4\/1210\/61433376\/ji1800081.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/202\/4\/1210\/61433376\/ji1800081.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T19:01:14Z","timestamp":1741114874000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/202\/4\/1210\/7953698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,2,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1800081","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,2]]},"published":{"date-parts":[[2019,2]]}}}