TWEAK/Fn14信号通路调控铁代谢与巨噬细胞极化在肺纤维化中的作用机制

刘丽红; 谢丽梅; 高彩茹; 李晨洋; 李峰; 马玉梅

doi:10.13898/j.cnki.issn.2097-5252.2025.07.006

TWEAK/Fn14信号通路调控铁代谢与巨噬细胞极化在肺纤维化中的作用机制

Mechanism of TWEAK/Fn14 signaling pathway in regulating iron metabolism and macrophage polarization in pulmonary fibrosis

摘要

摘要:
目的基于TWEAK/Fn14信号通路探究铁代谢与巨噬细胞极化中在肺纤维化中的可能作用机制。
方法将30只大鼠随机分为对照组、肺纤维化组及低表达TWEAK组，各10只。RT-qPCR检测肿瘤坏死因子样弱凋亡诱导因子(TWEAK)、成纤维细胞生长因子诱导蛋白14(Fn14)、FPN铁转运蛋白(FPN)、铁蛋白重链1(FTH1)、CD206、精氨酸酶1(Arg1)mRNA水平。Western blotting检侧TWEAK、Fn14、FPN、FTH1蛋白水平。HE染色检测肺组织病理结构。Masson染色检测肺组织纤维化情况。试剂盒检测肺组织中Fe²⁺、Fe³⁺水平。免疫组织化学染色检测肺组织中CD206、Arg1蛋白水平。
结果与对照组相比，肺纤维化组大鼠肺组织明显损伤，可见肺泡壁增厚、成纤维细胞增生肺泡结构异常紊乱，大量胶原纤维沉积，肺组织中TWEAK、Fn14、FPN、FTH1蛋白及mRNA水平均明显上升(P < 0.01)，Fe²⁺、Fe³⁺含量均明显增加(P < 0.01)，M2巨噬细胞标志物CD206、Arg1蛋白及mRNA水平均明显增加(P < 0.01)。与肺纤维化组相比，低表达TWEAK组肺组织病理损伤明显改善，胶原纤维沉积减少，肺组织中TWEAK、Fn14、FPN、FTH1蛋白及mRNA水平均明显降低(P < 0.01)，Fe²⁺、Fe³⁺含量均明显降低(P < 0.01)，CD206、Arg1蛋白及mRNA水平均明显降低(P < 0.01)。
结论下调TWEAK/Fn14信号通路可改善肺纤维化大鼠肺组织病理损伤及纤维化水平，这可能与该通路下调肺组织铁代谢并抑制M2巨噬细胞极化相关。

Abstract:
Objective To explore the possible mechanism of iron metabolism and macrophage polarization in pulmonary fibrosis based on TWEAK/Fn14 signaling pathway.
Methods Thirty rats were randomly divided into three groups: control group, pulmonary fibrosis group, and TWEAK low-expression group, with 10 rats in each group.RT-qPCR was used to measure mRNA levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), ferroportin (FPN), ferritin heavy chain 1 (FTH1), CD206, and rrginase 1 (Arg1).Western blotting was performed to determine protein levels of TWEAK, Fn14, FPN, and FTH1.HE staining was applied to assess pathological changes in lung tissue.Masson staining was employed to evaluate pulmonary fibrosis.Commercial kit was used to measure Fe²⁺ and Fe³⁺ levels in lung tissue.Immunohistochemistry was conducted to detect protein levels of CD206 and Arg1 in lung tissue.
Results Compared with the control group, the lung tissue of rats in the pulmonary fibrosis group was obviously damaged, with thickened alveolar wall, fibroblast proliferation, abnormal alveolar structure disorder, and extensive collagen fiber deposition; the protein and mRNA levels of TWEAK, Fn14, FPN, and FTH1 in lung tissue were significantly increased (P < 0.01);the levels of Fe²⁺ and Fe³⁺ were markedly elevated (P < 0.01);the protein and mRNA levels of M2 macrophage markers CD206 and Arg1 were significantly increased (P < 0.01).Compared with the pulmonary fibrosis group, the pathological injury of lung tissue in the low expression TWEAK group was significantly improved, the deposition of collagen fibers was reduced; the protein and mRNA levels of TWEAK, Fn14, FPN, and FTH1 in lung tissue were significantly decreased (P < 0.01);the levels of Fe²⁺ and Fe³⁺ were markedly decreased (P < 0.01);the protein and mRNA levels of CD206 and Arg1 were significantly decreased (P < 0.01).
Conclusions Down-regulation of TWEAK/Fn14 signaling pathway can improve the pathological injury and fibrosis level of lung tissue in rats with pulmonary fibrosis, which may be related to the down-regulation of iron metabolism in lung tissue and inhibition of M2 macrophage polarization.

HTML全文

参考文献(20)

施引文献

资源附件(0)