| First Author | Kwong EK | Year | 2019 |
| Journal | Dig Liver Dis | Volume | 51 |
| Issue | 8 | Pages | 1154-1163 |
| PubMed ID | 31003959 | Mgi Jnum | J:295717 |
| Mgi Id | MGI:6454486 | Doi | 10.1016/j.dld.2019.03.020 |
| Citation | Kwong EK, et al. (2019) The role of sphingosine kinase 2 in alcoholic liver disease. Dig Liver Dis 51(8):1154-1163 |
| abstractText | Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide. However, the exact mechanisms underlying ALD remain unclear. Previous studies reported that sphingosine kinase 2 (SphK2) plays an essential role in regulating hepatic lipid metabolism. In the current study, we demonstrate that compared to wild-type (WT) mice, SphK2 deficient (SphK2(-/-)) mice exhibited a greater degree of liver injury and hepatic lipid accumulation after feeding with an alcohol diet for 60 days. This is accompanied by a down-regulation of steroid 7-alpha-hydroxylase (Cyp7b1) and an up-regulation of pro-inflammatory mediators (Tnfalpha, F4/80, Il-1beta). In vitro experiments showed that alcohol induced SphK2 expression in mouse primary hepatocytes and cultured mouse macrophages. Furthermore, alcohol feeding induced a more severe intestinal barrier dysfunction in SphK2(-/-) mice than WT mice. Deficiency of SphK2 impaired the growth of intestinal organoids. Finally, SphK2 expression levels were down-regulated in the livers of human patients with alcoholic cirrhosis and hepatocellular carcinoma compared to healthy controls. In summary, these findings suggest that SphK2 is a crucial regulator of hepatic lipid metabolism and that modulating the SphK2-mediated signaling pathway may represent a novel therapeutic strategy for the treatment of ALD and other metabolic liver diseases. |
