Kizawa Ryusuke, Araya Jun, Fujita Yu
Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan.
Division of Next-Generation Drug Development, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
Inflamm Regen. 2023 Sep 21;43(1):45. doi: 10.1186/s41232-023-00295-1.
Idiopathic pulmonary fibrosis (IPF) is a progressive aging-related lung disease with a poor prognosis. Despite extensive research, the cause of IPF remains largely unknown and treatment strategies are limited. Proposed mechanisms of the pathogenesis of IPF are a combination of excessive accumulation of the extracellular matrix and dysfunctional lung tissue regeneration. Epithelial cell dysfunction, in addition to fibroblast activation, is considered a key process in the progression of IPF. Epithelial cells normally maintain homeostasis of the lung tissue through regulated proliferation, differentiation, cell death, and cellular senescence. However, various stresses can cause repetitive damage to lung epithelial cells, leading to dysfunctional regeneration and acquisition of profibrotic functions. The Hippo pathway is a central signaling pathway that maintains tissue homeostasis and plays an essential role in fundamental biological processes. Dysregulation of the Hippo pathway has been implicated in various diseases, including IPF. However, the role of the Hippo pathway in the pathogenesis of IPF remains unclear, particularly given the pathway's opposing effects on the 2 key pathogenic mechanisms of IPF: epithelial cell dysfunction and fibroblast activation. A deeper understanding of the relationship between the Hippo pathway and the pathogenesis of IPF will pave the way for novel Hippo-targeted therapies.
特发性肺纤维化（IPF）是一种与衰老相关的进行性肺部疾病，预后较差。尽管进行了广泛研究，但IPF的病因仍大多不明，治疗策略也有限。IPF发病机制的推测是细胞外基质过度积累和肺组织再生功能失调共同作用的结果。除了成纤维细胞活化外，上皮细胞功能障碍被认为是IPF进展中的关键过程。上皮细胞通常通过调控增殖、分化、细胞死亡和细胞衰老来维持肺组织的稳态。然而，各种应激可导致肺上皮细胞反复受损，导致再生功能失调并获得促纤维化功能。Hippo信号通路是维持组织稳态的核心信号通路，在基本生物学过程中起重要作用。Hippo信号通路失调与包括IPF在内的多种疾病有关。然而，Hippo信号通路在IPF发病机制中的作用仍不清楚，尤其是考虑到该信号通路对IPF的两个关键致病机制（上皮细胞功能障碍和成纤维细胞活化）具有相反作用。深入了解Hippo信号通路与IPF发病机制之间的关系将为新型Hippo靶向治疗铺平道路。
