Characterization of the properties of a selective, orally bioavailable autotaxin inhibitor in preclinical models of advanced stages of liver fibrosis.

ABSTRACT:

Background and purpose

Autotaxin (ATX) is a secreted phospholipase which hydrolyses lysophosphatidylcholine to generate lysophosphatidic acid (LPA). The extracellular signalling molecule LPA exerts its biological actions through activation of six GPCRs expressed in various cell types including fibroblasts. Multiple preclinical studies using knockout animals, LPA receptor antagonists or ATX inhibitors have provided evidence for a potential role of the ATX/LPA axis in tissue fibrosis. Despite growing evidence for a correlation between ATX levels and the degree of fibrosis in chronic liver diseases, including viral hepatitis and hepatocellular carcinoma, the role of ATX in non-alcoholic steatohepatitis (NASH) remains unclear.

Experimental approach

The relevance of ATX in the pa

SUBMITTER: Baader M 

PROVIDER: S-EPMC5787030 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature