下调CYTL1可通过TGF-β/CCN2通路抑制M2巨噬细胞极化,从而减轻博来霉素诱导的小鼠肺纤维化  

Down-regulation of CYTL1 Can Inhibit M2 Macrophage Polarization Through the TGF-β/CCN2 Pathway,Thereby Reducing Bleomycin-induced Pulmonary Fibrosis in Mice

作　　者：谢怡 王岩 XIE Yi;WANG Yan(Medical College of Shantou University,Shantou 515041,Guangdong,China;Department of Pathology,Shenzhen People′s Hospital,Shenzhen 518109,Guangdong,China)

机构地区：[1]汕头大学医学院,广东汕头515041 [2]深圳市人民医院病理科,广东深圳518109

出　　处：《系统医学》2025年第6期28-36,共9页Systems Medicine

摘　　要：目的研究细胞因子样1(cytokine-like 1,CYTL1)在特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)中的作用及其潜在机制。方法采用博莱霉素诱导的小鼠肺损伤和纤维化模型,检测CYTL1的表达水平,并通过基因敲除分析其对肺纤维化的影响。评估肺组织损伤、纤维化程度及巨噬细胞M2极化情况,探讨CYTL1对转化生长因子β(transforming growth factor-β,TGF-β)/结缔组织生长因子(connective tissue growth factor,CCN2)信号通路的调控作用。结果在博莱霉素诱导的小鼠模型中,CYTL1高表达。CYTL1的消融可减轻肺损伤和纤维化,并显著抑制巨噬细胞M2极化。此外,CYTL1通过调控TGF-β/CCN2信号通路影响肺纤维化进程。结论CYTL1在IPF进展中发挥关键作用,其高表达促进肺纤维化。抑制CYTL1可通过调节TGF-β/CCN2信号通路抑制巨噬细胞M2极化,从而减轻肺损伤和纤维化。CYTL1可能成为IPF治疗的潜在靶点。Objective To study the role of cytokine-like 1(CYTL1)in idiopathic pulmonary fibrosis(IPF)and its po-tential mechanism.Methods Bleomycin-induced mouse lung injury and fibrosis models were used to detect the ex-pression level of CYTL1,and its effect on pulmonary fibrosis was analyzed by gene knockout.To evaluate the degree of lung tissue injury,fibrosis and macrophage M2 polarization,and to explore the regulatory effect of CYTL1 on trans-forming growth factor-β(TGF-β)/connective tissue growth factor(CCN2)signaling pathway.Results In the bleomycin-induced mouse model,CYTL1 was highly expressed.The ablation of CYTL1 can reduce lung injury and fi-brosis,and significantly inhibit macrophage M2 polarization.In addition,CYTL1 affects the process of pulmonary fi-brosis by regulating the TGF-β/CCN2 signaling pathway.Conclusion CYTL1 plays a key role in the progression of IPF,and its high expression promotes pulmonary fibrosis.Inhibition of CYTL1 can inhibit macrophage M2 polariza-tion by regulating TGF-β/CCN2 signaling pathway,thereby reducing lung injury and fibrosis.CYTL1 may be a poten-tial target for IPF treatment.

关 键 词：细胞因子样1 特发性肺纤维化 肺损伤 TGF-β/CCN2信号通路 

分 类 号：R563[医药卫生—呼吸系统]