Altered lysophosphatidic acid (LPA) receptor expression during hepatic regeneration in a mouse model of partial hepatectomy.

ABSTRACT

BACKGROUND: Hepatic regeneration requires coordinated signal transduction for efficient restoration of functional liver mass. This study sought to determine changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1-6 expression in regenerating liver following two-thirds partial hepatectomy (PHx). METHODS: Liver tissue and blood were collected from male C57BL/6 mice following PHx. Circulating LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR mRNA and protein expression were determined. RESULTS: Circulating LPA increased 72 h after PHx and remained significantly elevated for up to 7 days post-PHx. Analysis of LPAR expression after PHx demonstrated significant increases in LPAR1, LPAR3 and LPAR6 mRNA and protein in a time-dependent manner for up to 7 days post-PHx. Conversely, LPAR2, LPAR4 and LPAR5 mRNA were barely detected in normal liver and did not significantly change after PHx. Changes in LPAR1 expression were confined to non-parenchymal cells following PHx. CONCLUSIONS: Liver regeneration following PHx is associated with significant changes in circulating LPA and hepatic LPAR1, LPAR3 and LPAR6 expression in a time- and cell-dependent manner. Furthermore, changes in LPA-LPAR post-PHx occur after the first round of hepatocyte division is complete.