CXCL5 inhibition improves kidney function by protecting renal tubular epithelial cells in diabetic kidney disease
Copyright © 2024. Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 268(2024) vom: 06. Nov., Seite 110369 |
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| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Chemokine CXC motif ligand 5 Diabetic kidney disease Fibrosis Inflammation Renal tubular epithelial cell Antibodies, Neutralizing Chemokine CXCL5 CXCL5 protein, human Cxcl5 protein, mouse |
| Zusammenfassung: | Copyright © 2024. Published by Elsevier Inc. Inflammation is one of exacerbating factors of diabetic kidney disease (DKD). Upregulated CXCL5 is found in clinical and experimental diabetes studies. This study aimed to investigate the impact and mechanism of CXCL5 on DKD. DKD patients with different levels of urine albumin-to-creatinine ratio were enrolled. Leprdb/db mice and CXCL5-knockout diabetic mice were used as mouse models for DKD. Human renal tubular epithelial cells were used for in vitro experiments. Circulating CXCL5 were increased in DKD patients compared to the non-DKD subjects. CXCL5 inhibition through CXCL5-neutralizing antibodies or genetic knockout improved kidney function and ameliorated tubular injury and renal fibrosis. In high-glucose-stimulated tubular epithelial cells, administration of CXCL5-neutralizing antibodies or siRNA resulted in reduced phospho-JNK/c-JUN/p65 and the downstream inflammatory, fibrotic, and apoptotic protein expressions. Administration of CXCR2 and JNK inhibitors impeded the CXCL5-induced tubular epithelial cell damages. In conclusion, these findings indicated that anti-CXCL5 strategies may be potential treatments for DKD |
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| Beschreibung: | Date Completed 04.11.2024 Date Revised 07.11.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2024.110369 |