南京医科大学学报（自然科学版）2025，Vol.45Issue(11)：1608-1615,1625,9.DOI:10.7655/NYDXBNSN250631
IFN-γ通过抑制SRC/Areg信号轴减轻克罗恩病肠纤维化
IFN-γ alleviates intestinal fibrosis in Crohn's disease through inhibiting the SRC/Areg signaling axis
摘要
Abstract
Objective:This study systematically investigates the regulatory role and mechanism of interferon-gamma(IFN-γ)in Crohn's disease(CD)-associated intestinal fibrosis.Methods:Intestinal fibroblasts were isolated from CD patients and treated with various cytokines[IFN-γ,interleukin(IL)-17A,IL-1β,IL-33,IL-36α,tumor necrosis factor(TNF)-α]in vitro.The mRNA expression level of amphiregulin(Areg)in human intestinal fibroblasts was detected using RT-PCR.Following treatment with 20 ng/mL IFN-γ for 48 h,transcriptome sequencing(RNA-seq)was performed,and a protein-protein interaction(PPI)network was constructed using the STRING database.Immunofluorescence was employed to detect myofibroblast markers such as alpha-smooth muscle actin(α-SMA)and antigen Kiel 67(Ki67),evaluating the effects of IFN-γ on the activation and proliferation of human intestinal fibroblasts.Results:Areg significantly promoted the activation,proliferation,and collagen synthesis of intestinal fibroblasts,whereas IFN-γ markedly suppressed Areg expression in intestinal fibroblasts and downregulated fibrosis-related genes including α-SMA,COL1A1,and COL6A1,while also inhibiting fibroblast proliferation and activation.RNA-seq analysis revealed that differentially expressed genes regulated by IFN-γ were significantly enriched in the extracellular matrix(ECM)remodeling pathway.PPI network analysis identified SRC as a core node,suggesting its potential role in mediating the anti-fibrotic effects of IFN-γ.Conclusion:Areg is a key mediator promoting intestinal fibrosis in CD.IFN-γ inhibits Areg expression through transcriptional regulation,and it is found that SRC may be a key effector molecule downstream of IFN-γ.IFN-γ may exert its anti-fibrotic effect by inhibiting the SRC/Areg signaling axis.These findings provide a theorectial basis for the development of anti-fibrotic strategies targeting the IFN-γ/SRC/Areg pathway.关键词
IFN-γ/双调蛋白/肠成纤维细胞/克罗恩病/肠纤维化Key words
IFN-γ/amphiregulin/intestinal fibroblast/Crohn's disease/intestinal fibrosis分类
临床医学引用本文复制引用
林俊杰,孙君健,王璐,王舒,张红杰,赵小静..IFN-γ通过抑制SRC/Areg信号轴减轻克罗恩病肠纤维化[J].南京医科大学学报（自然科学版）,2025,45(11):1608-1615,1625,9.基金项目
国家自然科学基金(82200582,82370535) （82200582,82370535）
中国博士后科学基金(2024M761212) （2024M761212）
