a study of Xu et al
Description
Fibrotic liver injury is a world-wide disease that results in loss of liver function, and currently there are no effective FDA approved treatment strategies for it yet. Here we show that LECT2 is a functional ligand of Tie1, which has been a mechanistically poorly characterized endothelial cell (EC)-specific orphan receptor for more than twenty years. By binding to Ig3 domain of Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling pathway, inhibits vascular endothelial cells migrations and tube formations. In vivo, LECT2 over-expression inhibits portal angiogenesis, promotes liver sinusoid capillarization, worsens fibrosis, whereas Lect2 KO induces portal angiogenesis, decreases liver sinusoid capillarization, attenuates fibrosis. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 shRNA treatment attenuates fibrosis. In additions, up-regulation of LECT2 is associated with advanced human liver fibrosis staging. We suggest that LECT2/Tie1 signaling pathway represents a valuable target for liver damage treatment, and plasma LECT2 can possibly serve as a diagnostic marker for liver fibrosis.