CXCL5 inhibition ameliorates acute kidney injury and prevents the progression from acute kidney injury to chronic kidney disease.

Autor:	Chang TT; Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Biomedical Industry Ph.D. Program, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan., Li SY; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan., Tsai MT; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan., Chiang CH; Division of Urology, Department of Surgery and Department of Research and Development, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.; Department of Urology, National Taiwan University Hospital, Taipei, Taiwan., Chen C; Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan., Chen JW; Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.; Division of Cardiology, Taipei Medical University Hospital, Taipei, Taiwan.; Faucalty of Medicine, Colleague of Medicine, Taipei Medical University, Taipei, Taiwan.; Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2024 Nov 20; Vol. 138 (22), pp. 1451-1466.
DOI:	10.1042/CS20241713
Abstrakt:	Acute kidney injury (AKI) increases the risk of chronic kidney disease (CKD). CXC motif chemokine ligand 5 (CXCL5) is up-regulated in kidney diseases. We aimed to investigate the direct effect of CXCL5 on the pathology of AKI. Serum and renal expression of CXCL5 were increased in animals with renal ischemia-reperfusion injury or unilateral ureteral obstruction. CXCL5-knockout mice exhibited reduced systemic oxidative stress and preserved renal function in the acute and chronic phases of AKI, as evidenced by reductions in serum BUN and creatinine levels, the urinary albumin-to-creatinine ratio, and the kidney-to-body weight ratio. CXCL5-knockout mice improved AKI-induced tubular injury and fibrosis, reduced renal macrophage infiltration, and reduced expression of NADPH oxidase and inflammatory and fibrotic proteins. CXCL5 activated p47 to up-regulate ROS generation and induce cellular damages through CXCR2. CXCL5 knockdown exerted antioxidative, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects on hypoxia-reoxygenation-stimulated renal proximal tubular epithelial cells. Clinical data indicated elevated circulating and renal CXCL5 in CKD patients, and renal CXCL5 was correlated with increased renal fibrosis and decreased estimated glomerular filtration rate. Altogether, CXCL5 levels increased in experimental AKI and clinical CKD, and in vivo and in vitro CXCL5 inhibition may reduce acute tubular injury and prevent the subsequent progression from AKI to CKD. (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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