Li Zhi-Hui, Chen Jun-Feng, Zhang Jing, Lei Zi-Ying, Wu Li-Li, Meng Shi-Bo, Wang Jia-Lei, Xiong Jing, Lin Deng-Na, Wang Jun-Yi, Gao Zhi-Liang, Lin Bing-Liang
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
Stem Cells. 2023 Dec 14;41(12):1171-1184. doi: 10.1093/stmcls/sxad069.
Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.
慢加急性肝衰竭（ACLF）是一种死亡率很高的严重疾病。巨噬细胞相关炎症在ACLF的发展中起关键作用。在我们之前的研究中，间充质干细胞（MSCs）治疗已被证明对ACLF有益；然而，其潜在机制仍不清楚。因此，使用小鼠骨髓来源的MSCs治疗ACLF小鼠模型，或与用脂多糖刺激的RAW264.7/J774A.1巨噬细胞共培养。分析组织学和血清学参数以及生存率以评估疗效。我们在体内和体外检测了Mer酪氨酸激酶（Mertk）、JAK1/STAT6、炎性细胞因子以及巨噬细胞极化标志物的变化。在ACLF小鼠中，MSCs改善了ACLF小鼠的肝功能和48小时生存率，并通过促进M2巨噬细胞极化和提高巨噬细胞中Mertk表达水平减轻了炎症损伤。这具有重要意义，因为Mertk通过JAK1/STAT6信号通路调节M2巨噬细胞极化。
