{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:18:23Z","timestamp":1790774303581,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T00:00:00Z","timestamp":1409270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Alport Syndrome Foundation, Macquarie, Pedersen family, Kidney Foundation of Canada"},{"name":"Alport Foundation of Australia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The glomerular filtration barrier comprises a fenestrated capillary endothelium, glomerular basement membrane and podocyte slit diaphragm. Over the past decade we have come to realise that permselectivity depends on size and not necessarily charge, that the molecular sieve depends on the podocyte contractile apparatus and is highly dynamic, and that protein uptake by proximal tubular epithelial cells stimulates signalling and the production of transcription factors and inflammatory mediators. Alport syndrome is the second commonest monogenic cause of renal failure after autosomal dominant polycystic kidney disease. Eighty per cent of patients have X\u2010linked disease caused by mutations in the <jats:italic>COL4A5<\/jats:italic> gene. Most of these result in the replacement of the collagen IV \u03b13\u03b14\u03b15 network with the \u03b11\u03b11\u03b12 heterotrimer. Affected membranes also have ectopic laminin and increased matrix metalloproteinase levels, which makes them more susceptible to proteolysis. Mechanical stress, due to the less elastic membrane and hypertension, interferes with integrin\u2010mediated podocyte\u2013GBM adhesion. Proteinuria occurs when urinary levels exceed tubular reabsorption rates, and initiates tubulointerstitial fibrosis. The glomerular mesangial cells produce increased TGF\u03b2 and CTGF which also contribute to glomerulosclerosis. Currently there is no specific therapy for Alport syndrome. However treatment with angiotensin converting enzyme (ACE) inhibitors delays renal failure progression by reducing intraglomerular hypertension, proteinuria, and fibrosis. Our greater understanding of the mechanisms underlying the GBM changes and their consequences in Alport syndrome have provided us with further novel therapeutic targets.<\/jats:p>","DOI":"10.1113\/jphysiol.2014.274449","type":"journal-article","created":{"date-parts":[[2014,8,9]],"date-time":"2014-08-09T01:37:19Z","timestamp":1407548239000},"page":"4013-4023","source":"Crossref","is-referenced-by-count":60,"title":["Alport syndrome: its effects on the glomerular filtration barrier and implications for future treatment"],"prefix":"10.1113","volume":"592","author":[{"given":"Judy","family":"Savige","sequence":"first","affiliation":[{"name":"University of Melbourne Royal Melbourne Hospital  Parkville Victoria 3050 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101086"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007030328"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.174"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2349482"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2520"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1074"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011040367"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64327-1"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00721.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/13816819709041431"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007090997"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00304.2006"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00362.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00393.2004"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2007.06.006"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081302"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2490-z"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00712.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00779.x"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2010.03.002"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.407"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(81)90571-4"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.15.8767"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e32830464de"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010030303"},{"key":"e_1_2_5_27_1","first-page":"21","article-title":"Adenovirus\u2010mediated gene transfer into kidney glomeruli using an ex vivo and in vivo kidney perfusion system \u2013 first steps towards gene therapy of Alport syndrome","volume":"3","author":"Heikkila P","year":"1996","journal-title":"Gene Ther"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.237"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.11.1897"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000141462.00630.76"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022296"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000090034.71205.74"},{"key":"e_1_2_5_33_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1681\/ASN.V114649","article-title":"X\u2010linked Alport syndrome: natural history in 195 families and genotype\u2010 phenotype correlations in males","volume":"11","author":"Jais JP","year":"2000","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283296044"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00173.2005"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119431"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.244"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007070829"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80057-X"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl810"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008060583"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2012.259"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009010123"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00037.2008"},{"key":"e_1_2_5_45_1","article-title":"Feasibility of repairing glomerular basement membrane defects in Alport syndrome","author":"Lin X","year":"2013","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.324"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.20.010403.094555"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004100871"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2272-z"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F84"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111270"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21401"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002400050094"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012121217"},{"key":"e_1_2_5_55_1","first-page":"184","article-title":"An unusual congenital and familial congenital malformative combination involving the eye and kidney","volume":"12","author":"Pierson M","year":"1963","journal-title":"J\u00a0Genet Hum"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0201"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050896"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.373"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012020148"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00234.x"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00744.x"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.102"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0730776100"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601436103"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2013.109"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020045"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002563"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39569"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008040434"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-008-0934-7"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176811"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5779"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80003-9"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22562"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00438.2010"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.06.015"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030100"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1159\/000424808"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2014.274449","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2014.274449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T13:45:30Z","timestamp":1697291130000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2014.274449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,29]]},"references-count":78,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2014,9,15]]}},"alternative-id":["10.1113\/jphysiol.2014.274449"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2014.274449","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,29]]}}}