Oncotarget

Research Papers:

Sphingosine kinase 1 mediates diabetic renal fibrosis via NF-κB signaling pathway: involvement of CK2α

Junying Huang, Jingyan Li, Zhiquan Chen, Jie Li, Qiuhong Chen, Wenyan Gong, Peiqing Liu and Heqing Huang _

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Oncotarget. 2017; 8:88988-89004. https://doi.org/10.18632/oncotarget.21640

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Abstract

Junying Huang1,2,*, Jingyan Li1,*, Zhiquan Chen1, Jie Li1, Qiuhong Chen1, Wenyan Gong1, Peiqing Liu1,3 and Heqing Huang1,3

1Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

2College of Life Sciences, Guangzhou University, Guangzhou 510006, China

3National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangzhou 51000, China

*These authors have contributed equally to this work

Correspondence to:

Heqing Huang, email: huangheq@mail.sysu.edu.cn

Keywords: sphingosine kinase 1, casein kinase 2α subunit, diabetic nephropathy, NF-κB pathway, renal fibrosis

Received: June 24, 2017     Accepted: August 26, 2017     Published: October 04, 2017

ABSTRACT

Sphingosine kinase 1 (SphK1) plays a pivotal role in regulating diabetic renal fibrotic factors such as fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1). Especially, activation of SphK1 is closely linked to the body inflammatory reaction. Casein kinase 2α subunit (CK2α), a protein kinase related to inflammatory reaction, influences diabetic renal fibrosis and expressions of FN and ICAM-1 via NF-κB pathway. However, the mechanism by which SphK1 mediates diabetic renal fibrosis has not yet fully elucidated. The current study is aimed to investigate if SphK1 mediates diabetic renal fibrotic pathological process via inflammatory pathway and activation of CK2α. The following findings were observed: (1) Expressions of SphK1 were upregulated in kidneys of diabetic mice and rats; (2) Knockdown of SphK1 expression suppressed high glucose (HG)-induced NF-κB nuclear translocation and expressions of FN and ICAM-1; (3) Compared with C57 diabetic mice, SphK1-/- diabetic mice exhibited less renal fibrotic lesions, FN accumulation and NF-κB nuclear accumulation in glomeruli of kidneys; (4) SphK1 mediated phosphorylation of CK2α, while CK2α knockdown depressed SphK1-induced activation of NF-κB pathway. This study indicates the essential role of SphK1 in regulating activation of CK2α and diabetic renal fibrotic pathological process via NF-κB.


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