Zhang Xinyue, Xu Zhihao, Chen Qi, Zhou Zhimin
Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China.
Front Cell Dev Biol. 2024 Oct 10;12:1450038. doi: 10.3389/fcell.2024.1450038. eCollection 2024.
Pulmonary fibrosis is a progressive interstitial lung disease associated with aging. The pathogenesis of pulmonary fibrosis remains unclear, however, alveolar epithelial cell injury, myofibroblast activation, and extracellular matrix (ECM) accumulation are recognized as key contributors. Moreover, recent studies have implicated cellular senescence, endothelial-mesenchymal transition (EndMT), and epigenetic modifications in the pathogenesis of fibrotic diseases. Various signaling pathways regulate pulmonary fibrosis, including the TGF-β, Notch, Wnt, Hedgehog, and mTOR pathways. Among these, the TGF-β pathway is extensively studied, while the Notch pathway has emerged as a recent research focus. The Notch pathway influences the fibrotic process by modulating immune cell differentiation (e.g., macrophages, lymphocytes), inhibiting autophagy, and promoting interstitial transformation. Consequently, inhibiting Notch signaling represents a promising approach to mitigating pulmonary fibrosis. In this review, we discuss the role of Notch signaling pathway in pulmonary fibrosis, aiming to offer insights for future therapeutic investigations.
肺纤维化是一种与衰老相关的进行性间质性肺疾病。尽管肺纤维化的发病机制仍不清楚，但肺泡上皮细胞损伤、肌成纤维细胞活化和细胞外基质（ECM）积累被认为是关键因素。此外，最近的研究表明细胞衰老、内皮-间质转化（EndMT）和表观遗传修饰参与了纤维化疾病的发病机制。多种信号通路调节肺纤维化，包括转化生长因子-β（TGF-β）、Notch、Wnt、Hedgehog和雷帕霉素靶蛋白（mTOR）通路。其中，TGF-β通路得到了广泛研究，而Notch通路则成为最近的研究热点。Notch通路通过调节免疫细胞分化（如巨噬细胞、淋巴细胞）、抑制自噬和促进间质转化来影响纤维化过程。因此，抑制Notch信号代表了一种减轻肺纤维化的有前景的方法。在这篇综述中，我们讨论了Notch信号通路在肺纤维化中的作用，旨在为未来的治疗研究提供见解。
