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

HPB (Oxford). 2014 Jun;16(6):534-42. doi: 10.1111/hpb.12176. Epub 2013 Sep 24.

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.

MeSH terms

  • Animals
  • Cell Proliferation
  • Gene Expression Regulation
  • Hepatectomy / methods*
  • Liver / metabolism
  • Liver / pathology
  • Liver / physiopathology
  • Liver / surgery*
  • Liver Regeneration*
  • Lysophospholipids / metabolism
  • Male
  • Mice, Inbred C57BL
  • Models, Animal
  • RNA, Messenger / metabolism
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Signal Transduction
  • Time Factors

Substances

  • Lysophospholipids
  • RNA, Messenger
  • Receptors, Lysophosphatidic Acid
  • lysophosphatidic acid