Merck

LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

Cell (2019-09-03)
Meng Xu, Hong-Hai Xu, Yuan Lin, Xiangnan Sun, Li-Jing Wang, Zhe-Ping Fang, Xue-Han Su, Xiang-Jing Liang, Yang Hu, Zhi-Min Liu, Yuanxiong Cheng, Yuanyuan Wei, Jiabin Li, Li Li, Hong-Juan Liu, Zhiqiang Cheng, Na Tang, Chao Peng, Tingting Li, Tengfei Liu, Liang Qiao, Dalei Wu, Yan-Qing Ding, Wei-Jie Zhou
ABSTRACT

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

MATERIALS
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Brand
Product Description

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