{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:37Z","timestamp":1785405577868,"version":"3.56.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Research Grants Council (RGC) of Hong Kong","award":["17108222"],"award-info":[{"award-number":["17108222"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["N_HKU7120\/24"],"award-info":[{"award-number":["N_HKU7120\/24"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RGC Joint Research Scheme"},{"DOI":"10.13039\/100010988","name":"Hong Kong Society of Nephrology Research","doi-asserted-by":"crossref","award":["2021"],"award-info":[{"award-number":["2021"]}],"id":[{"id":"10.13039\/100010988","id-type":"DOI","asserted-by":"crossref"}]},{"name":"L & T Charitable Foundation Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Excessive production of complement C5a detected in acute kidney injury (AKI) and during the development of chronic kidney disease (CKD) suggests its possible role in CKD progression, but the underlying mechanism remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Global, tubule- and myeloid-specific C5aR1 knockout and PMX53-treated mice were subjected to bilateral ischemia-reperfusion injury. Cultured kidney tubular epithelial cells and bone marrow-derived macrophages were used to analyse the underlying cellular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>C5aR1 deficiency specifically in kidney tubular cells, but not in myeloid cells, impaired M1 and favoured M2 macrophage polarization, resulting in attenuation of proinflammatory responses, oxidative stress, and the subsequent tubulointerstitial fibrosis during the progression from AKI to CKD. Deletion of tubular C5aR1 also induced mitochondrial biogenesis with increased mitochondrial DNA copy number and ATP content and reduced cell apoptosis via induction of autophagy in kidney tubules. In vitro, treatment with the C5aR1 antagonist PMX53 attenuated cell apoptosis by enhancing Bcl-2 interacting protein 3 (BNIP3)-regulated autophagy in C5a- and tumour necrosis factor-\u03b1-stimulated kidney tubular epithelial cells, which in turn modulated macrophage polarization and inflammatory responses via a paracrine mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data reveal a detrimental role of the C5a\/C5aR1 axis in AKI-to-CKD transition by triggering macrophage polarization towards a chronic inflammatory phenotype and disrupting mitochondrial homeostasis via the involvement of BNIP3-regulated autophagy in kidney tubular epithelial cells, leading to tubulointerstitial fibrosis and kidney dysfunction. Targeting C5aR1 may provide a promising therapeutic strategy for preventing CKD progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfag157","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:55:55Z","timestamp":1783598155000},"source":"Crossref","is-referenced-by-count":0,"title":["C5a\/C5aR1 mediates AKI\u2013CKD transition by enhancing autophagy"],"prefix":"10.1093","author":[{"given":"Jingyuan","family":"Ma","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Han","family":"Yiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah W Y","family":"Lok","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek K","family":"Lam","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar Neng","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuding","family":"Zhou","sequence":"additional","affiliation":[{"name":"Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , L\u00fcbeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-1941","authenticated-orcid":false,"given":"Sydney C W","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"2026073005115852000_bib1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: from mechanisms to therapeutic medicines","volume":"8","author":"Huang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2026073005115852000_bib2","first-page":"1238","volume":"389","author":"Webster","year":"2017","journal-title":"Chronic kidney disease. 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