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Chemokine CC motif ligand 4 (CCL4) is a proinflammatory chemokine that is up-regulated in kidney diseases. In the present study, we explored the role of CCL4 in the pathogenesis of AKI, focusing on its potential to modulate inflammatory and fibrotic responses through the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Mouse models of I\/R injury-induced AKI and lipopolysaccharide (LPS)-induced septic AKI were used for in vivo tests, and renal tubular epithelial cells were used for in vitro tests. Genetic knockout of CCL4 attenuated kidney dysfunction and structural damage in both the acute and chronic phases of I\/R injury-induced AKI in mice. CCL4 knockout also reduced the levels of inflammatory and fibrotic proteins such as interleukin-1\u03b2, interleukin-6, tumor necrosis factor-\u03b1, transforming growth factor-\u03b2, p-Smad2\/3, and collagen 1 in the kidney of AKI mice. In septic AKI mice, CCL4 knockout improved kidney dysfunction and kidney inflammation. In the in vitro experiments, the inhibition of CCL4 using CCL4 siRNA down-regulated hypoxia\/reperfusion- and LPS-induced inflammation in renal tubular cells. Furthermore, the administration of CCL4 could cause cellular inflammation and fibrosis through the STAT3 signaling pathway. These findings suggest that CCL4 plays a critical role in AKI pathophysiology, particularly in regulating inflammatory and fibrotic processes through STAT3. Our results suggest that targeting CCL4 may provide a novel therapeutic approach to mitigate AKI and prevent its progression to chronic kidney disease.<\/jats:p>","DOI":"10.1042\/cs20257231","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:26:46Z","timestamp":1772551606000},"page":"723-740","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of CCL4 prevents renal inflammation and fibrosis in acute kidney injury"],"prefix":"10.1042","volume":"140","author":[{"given":"Chih-Hung","family":"Chiang","sequence":"first","affiliation":[{"name":"1Division of Urology, Department of Surgery, Taipei City Hospital, Zhongxing Branch and Linsen Chinese Medicine and Kunming Branch, Taipei, Taiwan"},{"name":"2Department of Quality Management Center and Education and Research, Taipei City Hospital, Taipei, Taiwan"},{"name":"3Department of Urology, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Yun","family":"Lan","sequence":"additional","affiliation":[{"name":"4Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaw-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"4Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"5Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan"},{"name":"6Division of Cardiology, Taipei Medical University Hospital, Taipei, Taiwan"},{"name":"7Faucalty of Medicine, Colleague of Medicine, Taipei Medical University, Taipei, Taiwan"},{"name":"8Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-7029","authenticated-orcid":false,"given":"Ting-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"4Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"5Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan"},{"name":"9Ph.D. Program of Interdisciplinary Medicine and Biomedical Industry, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"10Microbiota Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"2026042809563752000_B1","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1213\/ANE.0000000000002369","article-title":"Perioperative acute kidney injury: an under-recognized problem","volume":"125","author":"Meersch","year":"2017","journal-title":"Anesth. 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