Bao Jiahui, Bao Wenjing, Song Yajie, Li Zhiliang, Kan Liang, Fu Jianhua, Zhang Dan
Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, P.R. China.
Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, China.
Cell Biosci. 2025 Jul 17;15(1):103. doi: 10.1186/s13578-025-01428-4.
The architecture of the mammalian lung is both intricate and distinct. The respiratory system consists of a complex network of semirigid airway tubes, stretching from the trachea to the alveoli, highly vascularized sacs responsible for gas exchange. This system demands precise regulation. The mammalian target of rapamycin (mTOR) functions as a receptor and regulatory hub for various cellular processes, including metabolism, proliferation, and autophagy, and plays a pivotal role in lung development and regeneration, continuing to influence cellular processes into early childhood. Over the past decade, studies have identified abnormally elevated mTOR activity in adult lung diseases such as acute lung injury and idiopathic pulmonary fibrosis, leading to the approval of mTOR inhibitors for clinical use. However, during fetal lung development and the postnatal period, mTOR often exhibits a dual role. Its dynamic expression requires careful adaptation to temporal and spatial variations. The safety and efficacy of mTOR inhibitors during these developmental windows remain uncertain, as the role of mTOR becomes increasingly complex in response to the dramatic changes in lung tissue. This review aims to analyze the regulatory mechanisms and functional roles of the mTOR pathway throughout various stages of lung development and adult pulmonary diseases, highlighting the need for caution in using mTOR inhibitors during critical developmental phases. Careful evaluation is essential when considering pharmaceutical interventions for abnormal lung development and pediatric pulmonary disorders.
哺乳动物肺的结构既复杂又独特。呼吸系统由一个复杂的半刚性气道管网络组成，从气管延伸到肺泡，肺泡是高度血管化的囊，负责气体交换。这个系统需要精确的调节。雷帕霉素的哺乳动物靶点（mTOR）作为各种细胞过程的受体和调节中心，包括代谢、增殖和自噬，在肺发育和再生中起关键作用，并在幼儿期继续影响细胞过程。在过去十年中，研究已经确定在急性肺损伤和特发性肺纤维化等成人肺部疾病中mTOR活性异常升高，这导致mTOR抑制剂被批准用于临床。然而，在胎儿肺发育和出生后时期，mTOR通常表现出双重作用。其动态表达需要仔细适应时间和空间的变化。由于在肺组织的剧烈变化中mTOR的作用变得越来越复杂，mTOR抑制剂在这些发育阶段的安全性和有效性仍然不确定。本综述旨在分析mTOR通路在肺发育和成人肺部疾病各个阶段的调节机制和功能作用，强调在关键发育阶段使用mTOR抑制剂时需要谨慎。在考虑对异常肺发育和儿童肺部疾病进行药物干预时，仔细评估至关重要。
