CXCL5 inhibition improves kidney function by protecting renal tubular epithelial cells in diabetic kidney disease

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2024-09-24 DOI:10.1016/j.clim.2024.110369

Ching Chen , Liang-Yu Lin , Yen-Wen Wu , Jaw-Wen Chen , Ting-Ting Chang

{"title":"CXCL5 inhibition improves kidney function by protecting renal tubular epithelial cells in diabetic kidney disease","authors":"Ching Chen , Liang-Yu Lin , Yen-Wen Wu , Jaw-Wen Chen , Ting-Ting Chang","doi":"10.1016/j.clim.2024.110369","DOIUrl":null,"url":null,"abstract":"<div><div>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. Lepr<sup>db/db</sup> 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.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110369"},"PeriodicalIF":4.5000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624004789","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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. Lepr^db/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.

Abstract Image

查看原文本刊更多论文

抑制 CXCL5 可保护糖尿病肾病患者的肾小管上皮细胞，从而改善肾功能。

炎症是糖尿病肾病（DKD）的恶化因素之一。在临床和实验性糖尿病研究中都发现了 CXCL5 的上调。本研究旨在探讨CXCL5对DKD的影响和机制。研究人员招募了不同尿白蛋白与肌酐比值水平的 DKD 患者。以 Leprdb/db 小鼠和 CXCL5 基因剔除糖尿病小鼠为 DKD 小鼠模型。体外实验使用人肾小管上皮细胞。与非 DKD 患者相比，DKD 患者循环中的 CXCL5 增加。通过 CXCL5 中和抗体或基因敲除抑制 CXCL5 可改善肾功能，减轻肾小管损伤和肾脏纤维化。在高葡萄糖刺激的肾小管上皮细胞中，给予 CXCL5 中和抗体或 siRNA 可减少磷酸-JNK/c-JUN/p65 以及下游炎症、纤维化和凋亡蛋白的表达。服用 CXCR2 和 JNK 抑制剂可抑制 CXCL5 诱导的肾小管上皮细胞损伤。总之，这些研究结果表明，抗CXCL5策略可能是治疗DKD的潜在方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.