The CXCL1-CXCR2 Axis Mediates Tubular Injury in Diabetic Nephropathy Through the Regulation of the Inflammatory Response.

Hanfen Tang,Lin Sun,Hong Liu,Yinghong Liu,Ming Yang,Panai Song

doi:10.3389/fphys.2021.782677

Abstract

Diabetic nephropathy (DN) is one of the most severe complications of diabetes. Inflammation mediated by inflammatory factors is thought to accelerate the progression of renal damage in DN. However, which inflammatory factors mediate the inflammatory response in DN remains unclear. In this study, we determined that the CXCL1-mediated inflammatory response may play an essential role in DN progression through bioassays. Subsequently, we observed that the expression of CXCL1 and its receptor (CXCR2) was significantly increased in the kidneys of mice with HFD + STZ induced diabetes and DN patients. In addition, inhibition of the CXCL1/CXCR2 axis by repertaxin alleviates renal inflammation and pathological damage in the kidneys of db/db mice. Finally, we noted that the CXCL1/CXCR2 axis might lead to inflammatory damage through phosphorylated NF-κB and further activate the NLRP3 inflammasome. Our results revealed the role of the CXCL1/CXCR2 axis in DN progression for the first time, which may be a novel therapeutic target for DN.

Highlights

With the development of the social economy, the number of diabetes patients worldwide is increasing year by year
Increased Inflammation and CXCL1/CXCR2 Expression Were Observed in the Kidneys of STZ-Induced Diabetic Mice and Diabetic Nephropathy Patients
The results implied that CXCL1/CXCR2 mediated inflammation may play a vital role in the occurrence and development of diabetic nephropathy

Summary

Introduction

With the development of the social economy, the number of diabetes patients worldwide is increasing year by year. Prolonged high blood glucose levels can lead to a range of microvascular complications, such as diabetic retinopathy (DR) (Cheung et al, 2010) and diabetic nephropathy (DN) (Yang et al, 2021a). DN has gradually become one of the leading causes of end-stage renal disease (ESRD), which has imposed severe economic burdens on society. Mitochondrial dysfunction (Yang et al, 2021b), oxidative stress (Jiang et al, 2020), and other factors are thought to be involved in DN development. Recent studies suggest that immune inflammation may be one of the core factors causing DN (Zheng and Zheng, 2016: Moreno et al, 2018; Yang et al, 2021a)

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