{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:47:03Z","timestamp":1789447623941,"version":"build-2803163510"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/01900"],"award-info":[{"award-number":["PI16\/01900"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00588"],"award-info":[{"award-number":["PI19\/00588"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00815"],"award-info":[{"award-number":["PI19\/00815"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI11\/00069"],"award-info":[{"award-number":["PI11\/00069"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/01467"],"award-info":[{"award-number":["PI15\/01467"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00378"],"award-info":[{"award-number":["PI18\/00378"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["IN607B 2016\/020"],"award-info":[{"award-number":["IN607B 2016\/020"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      In autosomal dominant polycystic kidney disease (ADPKD), interstitial inflammation promotes cyst progression. TWEAK is a TNF superfamily cytokine that regulates inflammatory responses, and its receptor, Fn14, is expressed in nephron epithelium. This paper describes TWEAK\u2019s role in ADPKD and its potential as a therapeutic target. The Fn14\/TWEAK axis is upregulated in human and mouse polycystic kidneys, and TWEAK administration in mice accelerates cyst progression, whereas anti-TWEAK treatment slows cyst growth, improving kidney function and survival. Anti-TWEAK antibodies restore several ADPKD-related pathways, such as proliferation and NF-\n                      <jats:italic toggle=\"yes\">\u03ba<\/jats:italic>\n                      B; slightly reduces fibrosis and apoptosis; and indirectly decreases macrophage recruitment. These findings identify the TWEAK signaling pathway as a new disease mechanism in ADPKD and a new possible therapeutic approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In autosomal dominant polycystic kidney disease (ADPKD), cyst development and enlargement lead to ESKD. Macrophage recruitment and interstitial inflammation promote cyst growth. TWEAK is a TNF superfamily (TNFSF) cytokine that regulates inflammatory responses, cell proliferation, and cell death, and its receptor Fn14 (TNFRSF12a) is expressed in macrophage and nephron epithelia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To evaluate the role of the TWEAK signaling pathway in cystic disease, we evaluated Fn14 expression in human and in an orthologous murine model of ADPKD. We also explored the cystic response to TWEAK signaling pathway activation and inhibition by peritoneal injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Meta-analysis of published animal-model data of cystic disease reveals mRNA upregulation of several components of the TWEAK signaling pathway. We also observed that TWEAK and Fn14 were overexpressed in mouse ADPKD kidney cysts, and TWEAK was significantly high in urine and cystic fluid from patients with ADPKD. TWEAK administration induced cystogenesis and increased cystic growth, worsening the phenotype in a murine ADPKD model. Anti-TWEAK antibodies significantly slowed the progression of ADPKD, preserved renal function, and improved survival. Furthermore, the anti-TWEAK cystogenesis reduction is related to decreased cell proliferation\u2013related MAPK signaling, decreased NF-\n                      <jats:italic toggle=\"yes\">\u03ba<\/jats:italic>\n                      B pathway activation, a slight reduction of fibrosis and apoptosis, and an indirect decrease in macrophage recruitment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies the TWEAK signaling pathway as a new disease mechanism involved in cystogenesis and cystic growth and may lead to a new therapeutic approach in ADPKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020071094","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T14:30:13Z","timestamp":1624285813000},"page":"1913-1932","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"32","clinical-trial-number":[{"clinical-trial-number":"nct00771329","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01499355","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01943513","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00738764","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-2139","authenticated-orcid":false,"given":"Adrian","family":"Cordido","sequence":"first","affiliation":[{"name":"Group of Genetics and Developmental Biology of Renal Diseases, Nephrology Laboratory (N\u00b011), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela Clinical Hospital Complex (CHUS), Santiago de Compostela, Spain"},{"name":"Genomic Medicine Group, Santiago de Compostela Clinical Hospital Complex (CHUS), Santiago de Compostela, Spain"},{"name":"RedInRen RETIC, Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5656-7223","authenticated-orcid":false,"given":"Laura","family":"Nu\u00f1ez-Gonzalez","sequence":"additional","affiliation":[{"name":"Group of Genetics and Developmental Biology of Renal Diseases, Nephrology Laboratory (N\u00b011), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela Clinical Hospital Complex (CHUS), Santiago de Compostela, Spain"},{"name":"Genomic Medicine Group, Santiago de Compostela Clinical Hospital Complex (CHUS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio M.","family":"Martinez-Moreno","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Jim\u00e9nez D\u00edaz Foundation (Health Research Institute and Autonomous University of Madrid), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaya","family":"Lamas-Gonzalez","sequence":"additional","affiliation":[{"name":"Group of Genetics and Developmental Biology of Renal Diseases, Nephrology Laboratory (N\u00b011), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela Clinical Hospital Complex (CHUS), Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rodriguez-Osorio","sequence":"additional","affiliation":[{"name":"RedInRen RETIC, Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Department of Nephrology and Hypertension, Jim\u00e9nez D\u00edaz Foundation (Health Research Institute and Autonomous University of Madrid), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-5236","authenticated-orcid":false,"given":"Maria 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