LECT2, also known as leukocyte cell-derived chemotaxin 2 or chondromodulin II (ChM-II), is a 16-kDa protein mainly produced by hepatocytes. It was first identified as a neutrophil chemotactic factor. LECT2 binds to several cell surface receptors like CD209a, Tie1, and Met, regulating various processes including inflammatory reaction, fibrogenesis, and tumor metastasis. It is involved in many physiological and pathological conditions, such as liver regeneration, neuronal development, and metabolic disorders [2,3].

In liver fibrosis, LECT2 was found to be a functional ligand of Tie1. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, while these changes were reversed in Lect2-KO mice. AAV9-LECT2 shRNA treatment significantly attenuates fibrosis, indicating that targeting LECT2/Tie1 signaling may be a potential therapeutic approach for liver fibrosis [1]. In a male mouse model of LPS-mediated NASH, LECT2 deletion exacerbated steatosis and macrophage infiltration, suggesting that LECT2 might protect against lipid accumulation and macrophage activation in the liver via p38 phosphorylation [4].

In conclusion, LECT2 is a pleiotropic protein with diverse functions. Model-based research, especially Lect2 KO mouse models, has revealed its crucial roles in liver-related diseases like fibrosis and NASH. These findings provide potential directions for developing LECT2-targeted therapies for such diseases.

References:

1. Xu, Meng, Xu, Hong-Hai, Lin, Yuan, Ding, Yan-Qing, Zhou, Wei-Jie. 2019. LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis. In Cell, 178, 1478-1492.e20. doi:10.1016/j.cell.2019.07.021. https://pubmed.ncbi.nlm.nih.gov/31474362/

2. Xie, Yuan, Fan, Kai-Wei, Guan, Shi-Xing, Gao, Yi, Zhou, Wei-Jie. 2022. LECT2: A pleiotropic and promising hepatokine, from bench to bedside. In Journal of cellular and molecular medicine, 26, 3598-3607. doi:10.1111/jcmm.17407. https://pubmed.ncbi.nlm.nih.gov/35656863/

3. Zhu, Sipin, Bennett, Samuel, Li, Yihe, Liu, Mei, Xu, Jiake. 2021. The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseases. In Journal of cellular physiology, 237, 480-488. doi:10.1002/jcp.30593. https://pubmed.ncbi.nlm.nih.gov/34550600/

4. Tanida, Ryota, Goto, Hisanori, Takayama, Hiroaki, Harada, Kenichi, Takamura, Toshinari. . LECT2 Deletion Exacerbates Liver Steatosis and Macrophage Infiltration in a Male Mouse Model of LPS-mediated NASH. In Endocrinology, 165, . doi:10.1210/endocr/bqae059. https://pubmed.ncbi.nlm.nih.gov/38781447/