Zhu Sipin, Bennett Samuel, Li Yihe, Liu Mei, Xu Jiake
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
J Cell Physiol. 2022 Jan;237(1):480-488. doi: 10.1002/jcp.30593. Epub 2021 Sep 22.
Leukocyte cell-derived chemotaxin-2 (LECT2 or LECT-2), also called chondromodulin II (ChM-II or CHM2) plays a versatile role in various tissues. It was first identified as a chemotactic factor to promote the migration of neutrophils. It was also reported as a hepatokine to regulate glucose metabolism, obesity, and nonalcoholic fatty liver disease. As a secreted factor, LECT2 binds to several cell surface receptors CD209a, Tie1, and Met to regulate inflammatory reaction, fibrogenesis, vascular invasion, and tumor metastasis in various cell types. As an intracellular molecule, it is associated with LECT2-mediated amyloidosis, in which LECT2 misfolding results in insoluble fibrils in multiple tissues such as the kidney, liver, and lung. Recently, LECT2 was found to be associated with the development of rheumatoid arthritis and osteoarthritis, involving the dysregulation of osteoclasts, mesenchymal stem cells, osteoblasts, chondrocytes, and endothelial cells in the bone microenvironment. LECT2 is implicated in the development of cancers, such as hepatocellular carcinoma via MET-mediated PTP1B/Raf1/ERK signaling pathways and is proposed as a biomarker. The mechanisms by which LECT2 regulates diverse pathogenic conditions in various tissues remain to be fully elucidated. Further research to understand the role of LECT2 in a tissue tropism-dependent manner would facilitate the development of LECT2 as a biomarker for diagnosis and therapeutic target.
白细胞衍生趋化因子2（LECT2或LECT - 2），也称为软骨调节素II（ChM - II或CHM2），在多种组织中发挥着多种作用。它最初被鉴定为一种促进中性粒细胞迁移的趋化因子。它还被报道为一种调节葡萄糖代谢、肥胖和非酒精性脂肪肝病的肝因子。作为一种分泌因子，LECT2与几种细胞表面受体CD209a、Tie1和Met结合，以调节各种细胞类型中的炎症反应、纤维生成、血管侵袭和肿瘤转移。作为一种细胞内分子，它与LECT2介导的淀粉样变性有关，其中LECT2错误折叠导致在肾脏、肝脏和肺等多个组织中形成不溶性纤维。最近，发现LECT2与类风湿性关节炎和骨关节炎的发展有关，涉及骨微环境中破骨细胞、间充质干细胞、成骨细胞、软骨细胞和内皮细胞的失调。LECT2与癌症的发展有关，例如通过MET介导的PTP1B/Raf1/ERK信号通路与肝细胞癌有关，并被提议作为一种生物标志物。LECT2在各种组织中调节多种致病状况的机制仍有待充分阐明。进一步以组织嗜性依赖的方式了解LECT2的作用的研究将有助于将LECT2开发为诊断生物标志物和治疗靶点。
