CXCL16 regulates cisplatin-induced acute kidney injury.

Hua Liang,Zhengmao Zhang,Liqun He,Yanlin Wang

doi:10.18632/oncotarget.9386

Hua Liang, Zhengmao Zhang + Show 2 more

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https://doi.org/10.18632/oncotarget.9386

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Abstract

The pathogenesis of cisplatin-induced acute kidney injury (AKI) is characterized by tubular cell apoptosis and inflammation. However, the molecular mechanisms are not fully understood. We found that CXCL16 was induced in renal tubular epithelial cells in response to cisplatin-induced AKI. Therefore, we investigated whether CXCL16 played a role in cisplatin–induced tubular cell apoptosis and inflammation. Wild-type and CXCL16 knockout mice were administrated with vehicle or cisplatin at 20 mg/kg by intraperitoneal injection. CXCL16 knockout mice had lower blood urea nitrogen and less tubular damage following cisplatin-induced AKI as compared with wild-type mice. Genetic disruption of CXCL16 reduced tubular epithelial cell apoptosis and decreased caspase-3 activation. Furthermore, CXCL16 deficiency inhibited infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was associated with reduced expression of the proinflammatory cytokines in the kidneys. Taken together, our results indicate that CXCL16 plays a crucial role in the pathogenesis of cisplatin–induced AKI through regulation of apoptosis and inflammation and maybe a novel therapeutic target for cisplatin-induced AKI.

Highlights

Cisplatin is one of the most effective and widely used chemotherapeutic agents for the treatment of a variety of solid tumors [1]
We first determined if CXC chemokine ligand 16 (CXCL16) is induced in the kidney in a mouse model of acute kidney injury (AKI) induced by cisplatin
Using real-time reverse transcription-PCR (RT-PCR), we found that the mRNA levels of CXCL16 were upregulated significantly in the kidneys of cisplatin-treated wild-type (WT) mice compared with vehicle controls (Figure 1A)

Summary

Introduction

Cisplatin (cis-Diamminedichloroplatinum II) is one of the most effective and widely used chemotherapeutic agents for the treatment of a variety of solid tumors [1]. One of the major side effects of cisplatin is acute kidney injury (AKI), which often limits the clinical utility of cisplatin [2, 3]. The transmembrane form has a transmembrane structure that functions as an adhesion molecule for CXCR6-expressing cells and serves as a scavenger receptor for oxidized lipoprotein and bacteria. CXCL16 is expressed at a low level in epithelial cells in the normal kidney and play a crucial role in regulating inflammation and tissue injury [10, 11]. We have recently demonstrated that CXCL16 contributes to chronic renal injury and fibrosis by recruiting fibrocytes, macrophages and T cells into the kidney [12, 13]. Our results have shown that genetic disruption of CXCL16 protects the kidney from cisplatin-induced AKI through inhibiting apoptosis and inflammation

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