{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:56:37Z","timestamp":1792180597873,"version":"4.4.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/STaR\/0029\/2017"],"award-info":[{"award-number":["NMRC\/STaR\/0029\/2017"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018059","name":"Tanoto Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018059","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"NMRC","doi-asserted-by":"crossref","award":["NMRC\/OFYIRG\/0053\/2017"],"award-info":[{"award-number":["NMRC\/OFYIRG\/0053\/2017"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001674","name":"Leducq Foundation","doi-asserted-by":"publisher","award":["16CVD03"],"award-info":[{"award-number":["16CVD03"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union Horizon 2020 Research and Innovation Program","award":["AdG788970"],"award-info":[{"award-number":["AdG788970"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alport syndrome is a genetic disorder characterized by a defective glomerular basement membrane, tubulointerstitial fibrosis, inflammation, and progressive renal failure. IL-11 was recently implicated in fibrotic kidney disease, but its role in Alport syndrome is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We determined IL-11 expression by molecular analyses and in an Alport syndrome mouse model. We assessed the effects of a neutralizing IL-11 antibody (\u00d7203) versus an IgG control in\n                      <jats:italic toggle=\"yes\">Col4a3\u2212\/\u2212<\/jats:italic>\n                      mice (lacking the gene encoding a type IV collagen component) on renal tubule damage, function, fibrosis, and inflammation. Effects of \u00d7203, the IgG control, an angiotensin-converting enzyme (ACE) inhibitor (ramipril), or ramipril+X203 on lifespan were also studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In\n                      <jats:italic toggle=\"yes\">Col4a3\u2212\/\u2212<\/jats:italic>\n                      mice, as kidney failure advanced, renal IL-11 levels increased, and IL-11 expression localized to tubular epithelial cells. The IL-11 receptor (IL-11RA1) is expressed in tubular epithelial cells and podocytes and is upregulated in tubular epithelial cells of\n                      <jats:italic toggle=\"yes\">Col4a3\u2212\/\u2212<\/jats:italic>\n                      mice. Administration of \u00d7203 reduced albuminuria, improved renal function, and preserved podocyte numbers and levels of key podocyte proteins that are reduced in\n                      <jats:italic toggle=\"yes\">Col4a3\u2212\/\u2212<\/jats:italic>\n                      mice; these effects were accompanied by reduced fibrosis and inflammation, attenuation of epithelial-to-mesenchymal transition, and increased expression of regenerative markers. X203 attenuated pathogenic ERK and STAT3 pathways, which were activated in\n                      <jats:italic toggle=\"yes\">Col4a3\u2212\/\u2212<\/jats:italic>\n                      mice. The median lifespan of\n                      <jats:italic toggle=\"yes\">Col4a3\u2212\/\u2212<\/jats:italic>\n                      mice was prolonged 22% by ramipril, 44% with \u00d7203, and 99% with ramipril+X203.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In an Alport syndrome mouse model, renal IL-11 is upregulated, and neutralization of IL-11 reduces epithelial-to-mesenchymal transition, fibrosis, and inflammation while improving renal function. Anti-IL-11 combined with ACE inhibition synergistically extends lifespan. This suggests that a therapeutic approach targeting IL-11 holds promise for progressive kidney disease in Alport syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021040577","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T15:45:16Z","timestamp":1644421516000},"page":"718-730","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":52,"title":["A Neutralizing IL-11 Antibody Improves Renal Function and Increases Lifespan in a Mouse Model of Alport Syndrome"],"prefix":"10.1681","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9404-7608","authenticated-orcid":false,"given":"Anissa A.","family":"Widjaja","sequence":"first","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamini G.","family":"Shekeran","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Adami","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"},{"name":"Cardiovascular and Metabolic Sciences, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce G Wei","family":"Ting","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"Tan","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-1656","authenticated-orcid":false,"given":"Sivakumar","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-5129","authenticated-orcid":false,"given":"Sze Yun","family":"Lim","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puay Hoon","family":"Tan","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"},{"name":"Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore"},{"name":"Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Sciences, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany"},{"name":"Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Coffman","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart A.","family":"Cook","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore"},{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore"},{"name":"MRC-London Institute of Medical Sciences, Hammersmith Hospital Campus, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,4]]},"reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1056\/NEJMra022296","article-title":"Alport\u2019s syndrome, Goodpasture\u2019s syndrome, and type IV collagen","volume":"348","author":"Hudson","year":"2003","journal-title":"N Engl J Med"},{"key":"B2-20250823","doi-asserted-by":"crossref","first-page":"26033","DOI":"10.1016\/S0021-9258(19)74270-7","article-title":"Type IV collagen: structure, gene organization, and role in human diseases. 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