{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:59:30Z","timestamp":1793581170994,"version":"4.5.0"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NIDDK","award":["DK114558"],"award-info":[{"award-number":["DK114558"]}]},{"name":"Weill Cornell Medical College","award":["Rohr Family Clinical Scholar Award"],"award-info":[{"award-number":["Rohr Family Clinical Scholar Award"]}]},{"DOI":"10.13039\/100006792","name":"The Hartwell Foundation","doi-asserted-by":"crossref","award":["Individual Biomedical Research Award"],"award-info":[{"award-number":["Individual Biomedical Research Award"]}],"id":[{"id":"10.13039\/100006792","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:p>\n                    Systemic iron metabolism is disrupted in chronic kidney disease (CKD). However, little is known about local kidney iron homeostasis and its role in kidney fibrosis. Kidney-specific effects of iron therapy in CKD also remain elusive. Here, we elucidate the role of macrophage iron status in kidney fibrosis and demonstrate that it is a potential therapeutic target. In CKD, kidney macrophages exhibited depletion of labile iron pool (LIP) and induction of transferrin receptor 1, indicating intracellular iron deficiency. Low LIP in kidney macrophages was associated with their defective antioxidant response and proinflammatory polarization. Repletion of LIP in kidney macrophages through knockout of ferritin heavy chain (\n                    <jats:italic>Fth1<\/jats:italic>\n                    ) reduced oxidative stress and mitigated fibrosis. Similar to\n                    <jats:italic>Fth1<\/jats:italic>\n                    knockout, iron dextran therapy, through replenishing macrophage LIP, reduced oxidative stress, decreased the production of proinflammatory cytokines, and alleviated kidney fibrosis. Interestingly, iron markedly decreased TGF-\u03b2 expression and suppressed TGF-\u03b2\u2013driven fibrotic response of macrophages. Iron dextran therapy and FtH suppression had an additive protective effect against fibrosis. Adoptive transfer of iron-loaded macrophages alleviated kidney fibrosis, validating the protective effect of iron-replete macrophages in CKD. Thus, targeting intracellular iron deficiency of kidney macrophages in CKD can serve as a therapeutic opportunity to mitigate disease progression.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.159235","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T12:00:44Z","timestamp":1668686444000},"source":"Crossref","is-referenced-by-count":52,"title":["Iron therapy mitigates chronic kidney disease progression by regulating intracellular iron status of kidney macrophages"],"prefix":"10.1172","volume":"8","author":[{"given":"Edwin","family":"Patino","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8236-3440","authenticated-orcid":true,"given":"Divya","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Z.","family":"Vance","sequence":"additional","affiliation":[{"name":"Iron Research Laboratory, Lindsley Kimball Research Institute, New York Blood Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Antypiuk","sequence":"additional","affiliation":[{"name":"Iron Research Laboratory, Lindsley Kimball Research Institute, New York Blood Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-4860","authenticated-orcid":true,"given":"Rie","family":"Uni","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantalle","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo G.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA."},{"name":"College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahd","family":"Jaouni","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA."},{"name":"Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vinchi","sequence":"additional","affiliation":[{"name":"Iron Research Laboratory, Lindsley Kimball Research Institute, New York Blood Center, New York, New York, USA."},{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA."},{"name":"New York-Presbyterian Hospital, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-5418","authenticated-orcid":true,"given":"Oleh","family":"Akchurin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA."},{"name":"New York-Presbyterian Hospital, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.17.2038"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfz192"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01150114"},{"key":"B4","unstructured":"McMurray J, et al. 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