Sphingosine kinase 1 inhibition decreases the epithelial-mesenchymal transition and ameliorates renal fibrosis via modulating NF- κB signaling.

This study aimed to investigate the role of Sphingosine kinase 1 (SphK1) on epithelial-mesenchymal transition (EMT) in renal fibrosis and the potential regulatory mechanisms. In the present study, unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model was established. HE and Masson staining were employed to detect the pathological change and fibrous deposition in renal tissues respectively. Moreover, the expression of SphK1, EMT relative proteins including E-cadherin (E-cad), N-cadherin (N-cad) and vimentin as well as fibrosis marker protein α-smooth muscle actin (α-SMA) were measured by immunohistochemistry and Western blot, respectively. In vitro, SphK1 silencing was generated in TGF-β induced human renal tubular epithelial HK-2 cells. Immunofluorescence staining was applied to examine the expression of α-SMA, then the levels of EMT relative proteins and NF-κB signaling were measured using Western blot. The results revealed that notably tubulointerstitial damage and fibrous deposition were detected in the UUO mouse renal tissues. The expression level of E-cad and SphK1 were decreased coupled with an increase of N-cad, vimentin and α-SMA expression. Furthermore, after knockdown of SphK1 in TGF-β induced HK-2 cells, the E-cad expression was up-regulated while N-cad, vimentin and α-SMA expression were down-regulated remarkably. In addition, the expression levels of phospho-NF-κB p65 (p-NF-κB p65) and p-IκB-α were lowered significantly following Sp...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research