Hua Ruheng, Yu Pengfei, Zheng Wanting, Wu Nuwa, Yu Wangjianfei, Kong Qingyu, He Jun, Qin Lei
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Oct 23;56(12):1761-1773. doi: 10.3724/abbs.2024191.
Tim-1 (T-cell immunoglobulin and mucin domain 1), also known as Kim-1 (kidney injury molecule 1) or hepatitis A virus cellular receptor 1 (HAVCR1), is a transmembrane protein expressed on various immune and epithelial cells. It plays a role in modulating inflammatory and immune responses. In this study, we find that Tim-1 is overexpressed in hepatocellular carcinoma (HCC) samples and that its expression is significantly correlated with postoperative survival. Bulk RNA sequencing reveals a general upregulation of extracellular matrix-related genes in HCC tissues with Tim-1 overexpression. The results of the cell and experiments reveal that Tim-1 in HCC not only affects biological processes such as the proliferation, migration, and invasion of HCC cells but also broadly promotes extracellular matrix processes by influencing cytokine secretion. Further studies demonstrate that Tim-1 mediates the activation of hepatic stellate cells and upregulates Th1 and Th2 cytokines, thereby promoting HCC progression. Thus, Tim-1 may represent a novel target for future interventions in HCC and liver fibrosis.
Tim-1（T细胞免疫球蛋白和粘蛋白结构域1），也被称为Kim-1（肾损伤分子1）或甲型肝炎病毒细胞受体1（HAVCR1），是一种在多种免疫细胞和上皮细胞上表达的跨膜蛋白。它在调节炎症和免疫反应中发挥作用。在本研究中，我们发现Tim-1在肝细胞癌（HCC）样本中过表达，且其表达与术后生存率显著相关。批量RNA测序显示，在Tim-1过表达的HCC组织中，细胞外基质相关基因普遍上调。细胞实验结果表明，HCC中的Tim-1不仅影响HCC细胞的增殖、迁移和侵袭等生物学过程，还通过影响细胞因子分泌广泛促进细胞外基质过程。进一步研究表明，Tim-1介导肝星状细胞的激活并上调Th1和Th2细胞因子，从而促进HCC进展。因此，Tim-1可能是未来HCC和肝纤维化干预的新靶点。
