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

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 2 alpha subunit (CK2 alpha), a protein kinase related to inflammatory reaction, influences diabetic renal fibrosis and expressions of FN and ICAM-1 via NF-kappa B 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 CK2 alpha. 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-kappa B 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-kappa B nuclear accumulation in glomeruli of kidneys; (4) SphK1 mediated phosphorylation of CK2 alpha, while CK2 alpha knockdown depressed SphK1-induced activation of NF-kappa B pathway. This study indicates the essential role of SphK1 in regulating activation of CK2 alpha and diabetic renal fibrotic pathological process via NF-kappa B.