Jiang Yu, Wang Zhongzhen, Hu Jinying, Wang Wei, Zhang Na, Gao Lili
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Aging (Albany NY). 2023 Sep 18;15(18):9572-9589. doi: 10.18632/aging.205036.
Idiopathic pulmonary fibrosis (IPF), a fatal disorder associated with aging, has a terrible prognosis. However, the potential causes of IPF remain a riddle. In this study, we designed to explore whether the modification of the core fucosylation (CF) can ameliorate pulmonary fibrosis by targeting alveolar epithelial cells (AECs) senescence. First, we verified that cellular senescence occurs in the bleomycin-induced lung fibrosis mice models and CF modifications accompanying senescent AECs in pulmonary fibrosis. Next, both gain- and loss- of function research on CF were performed to elucidate its role in promoting AECs senescence and triggering pulmonary fibrosis . Notably, using alveolar epithelial cell-specific FUT8 conditional knockout mouse models, however, inhibition of cellular senescence by deleting the FUT8 gene could attenuate pulmonary fibrosis . Finally, blocking the CF modification of transforming growth factor -β type I receptor (TGF-βR I) could reduce the activation of downstream transforming growth factor -β (TGF-β) pathways in AECs senescence both and . This study reveals that CF is a crucial interventional target for the treatment of pulmonary fibrosis. Blocking CF modification contributes importantly to inhibiting AECs senescence resulting in pulmonary fibrosis lessen.
特发性肺纤维化（IPF）是一种与衰老相关的致命性疾病，预后很差。然而，IPF的潜在病因仍是一个谜。在本研究中，我们旨在探讨核心岩藻糖基化（CF）修饰是否可通过靶向肺泡上皮细胞（AECs）衰老来改善肺纤维化。首先，我们证实细胞衰老发生在博来霉素诱导的肺纤维化小鼠模型中，且肺纤维化中衰老的AECs伴有CF修饰。接下来，我们对CF进行了功能获得和功能丧失研究，以阐明其在促进AECs衰老和引发肺纤维化中的作用。值得注意的是，使用肺泡上皮细胞特异性FUT8条件性敲除小鼠模型，通过删除FUT8基因抑制细胞衰老可减轻肺纤维化。最后，阻断转化生长因子-βⅠ型受体（TGF-βR I）的CF修饰可减少AECs衰老中及下游转化生长因子-β（TGF-β）信号通路的激活。本研究表明，CF是治疗肺纤维化的关键干预靶点。阻断CF修饰对抑制导致肺纤维化减轻的AECs衰老具有重要作用。
