Professor ZHOU Wei-Jie and his team in the School of Basic Medical Sciences of the Southern Medical University have identified LECT2 as a functional ligand for Endothelial Cell (EC)-specific orphan receptor Tie1 and provided valuable insights into a potential role of LECT2/Tie1 signaling in angiogenesis/sinusoid capillarization and liver fibrogenesis. The innovation was recently published in the international scientific journal Cell.
Liver fibrosis is a condition with excessive deposition of extracellular matrixes such as collagens and fibronectin in the liver tissue as a result of repeated liver injury often seen in patients with chronic liver diseases (CLDs). Without effective intervention, liver fibrosis leads to liver cirrhosis, one of the most common causes of death worldwide. So far, there is no FDA approved drug for the treatment of liver fibrosis. ZHOU’s studies has brought new understanding and strategy for the treatment of liver fibrosis.
One of the most important findings in this study is the identification of LECT2 as a ligand of Tie1, an EC-specific orphan receptor. They clarified that LECT2 induces Tie1 dephosphorylation and Tie2 phosphorylation; activates MAPK/PPAR/MMP/VE-cadherin signaling pathway; inhibits EC migration and tube formation; inhibits portal angiogenesis; and induces sinusoid capillarization. All of these events lead to liver fibrogenesis.
More importantly, ZHOU’s studies update our understanding of the role of vascular changes during liver fibrogenesis. They suggest that portal angiogenesis and sinusoid capillarization play divergent roles during liver fibrogenesis: portal angiogenesis attenuates fibrogenesis, whereas sinusoid capillarization promotes fibrogenesis. As such, they propose that a combinatorial use of promoting portal angiogenesis and simultaneous inhibition of sinusoid capillarization would help achieve better therapeutic effects for liver fibrosis. In this regard, LECT2-Tie1 signaling pathway may represent a valuable target for liver fibrosis treatment.
Overcoming the bottleneck of liver fibrosis treatment will bring the possibility for the treatment of CLDs caused by various etiologies. ZHOU and his team have been committed to clarifying the mechanism of liver fibrogenesis, hoping to find a reliable way to treat liver fibrosis.