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CXCL16 is activated by p-JNK and is involved in H 2 O 2-induced HK-2 cell injury via p-ERK signaling

CXCL16 is activated by p-JNK and is involved in H 2 O 2-induced HK-2 cell injury via p-ERK signaling

Weitao Zhang, Ting Hua, Jiawei Li, Long Zheng, Yifan Wang, Ming Xu, Guisheng Qi

Am J Transl Res. 2018 Nov 15;10(11):3723-3732.

PMID: 30662622

Abstract:

Acute kidney injury (AKI) leads to an abrupt deterioration of renal function. CXC chemokine ligand 16 (CXCL16) is a CXC-soluble chemokine and a cell surface scavenger receptor that is involved in tissue injury and inflammation. It is induced in AKI patients, but the molecular mechanism remains unclear. In this study, we have worked to determine the function of CXCL16 and to investigate the involvement of ERK and JNK signaling in AKI. We used H2O2 and recombinant human CXCL16 protein (rh CXCL16) to treat the human renal tubular epithelial cell line, HK-2, in vitro. The present results indicate that H2O2 inhibits proliferation, induces apoptosis, and up-regulates expression of CXCL16 and the CXCL16 receptor, CXCR6, in HK-2 cells. Furthermore, H2O2-induced proliferation inhibition, apoptosis, and inflammation in HK-2 cells were ameliorated by NAC (N-acetyl cysteine, the ROS scavenger) and SP600125 (the JNK inhibitor). The expression levels of CXCL16 and CXCR6 were also positively correlated with the phosphorylation level of JNK (p-JNK). Additionally, rh CXCL16 treatment led to effects like those of H2O2 treatment in HK-2 cells, with symptoms being effectively improved by CXCR6 siRNA and the ERK inhibitor (PD98059). In addition, rh CXCL16-induced HK-2 cell apoptosis, inflammation, and collagen deposition were lessened by CXCR6 siRNA and PD98059 treatment. In summary, the present results have indicated that CXCL16 is involved in H2O2-induced HK-2 cell injury, that CXCL16 is activated by p-JNK, and that the regulatory function of CXCL16 is involved in the phosphorylation of ERK.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248567	CXCL16 human			Price

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