LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis
| Autor: | Yang Hu, Liang Qiao, Jiabin Li, Li Li, Chao Peng, Xiangnan Sun, Tengfei Liu, Xue-Han Su, Yanqing Ding, Yuan Lin, Zhi-Min Liu, Hong-Juan Liu, Meng Xu, Hong-Hai Xu, Weijie Zhou, Zheping Fang, Zhiqiang Cheng, Yuanyuan Wei, Lijing Wang, Na Tang, Xiang-Jing Liang, Yuanxiong Cheng, Tingting Li, Dalei Wu |
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| Rok vydání: | 2018 |
| Předmět: |
Liver Cirrhosis
Angiogenesis General Biochemistry Genetics and Molecular Biology TIE1 Receptors TIE Small hairpin RNA 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Fibrosis medicine Animals Humans 030304 developmental biology Orphan receptor 0303 health sciences biology Endothelial Cells medicine.disease Angiopoietin receptor Capillaries Endothelial stem cell Mice Inbred C57BL HEK293 Cells Liver Cancer research biology.protein Hepatocytes Intercellular Signaling Peptides and Proteins 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Cell. 178(6) |
| ISSN: | 1097-4172 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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