Journal
PHARMACOLOGICAL RESEARCH
Volume 169, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.105635
Keywords
Idiopathic pulmonary fibrosis; Hippo/YAP pathway; Mechanotransduction; Alveolar regeneration; Reverse fibrosis
Categories
Funding
- National Natural Science Foundation of China [81703505]
- Special Fund for Military Medical Science [BWS16J007]
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IPF is a progressive disease characterized by an inexorable decline in lung function, involving multiple positive feedback loops and the crucial role of the Hippo/YAP signaling pathway. YAP/TAZ plays a key role in pulmonary fibrosis and alveolar regeneration by regulating cell proliferation and extracellular matrix deposition through different signaling pathways.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by an inexorable decline in lung function. The development of IPF involves multiple positive feedback loops; and a strong support role of the Hippo/YAP signalling pathway, which is essential for regulating cell proliferation and organ size, in IPF pathogenesis has been unveiled recently in cell and animal models. YAP/TAZ contributes to both pulmonary fibrosis and alveolar regeneration via the conventional Hippo/YAP signalling pathway, G protein-coupled receptor signalling, and mechanotransduction. Selectively inhibiting YAP/TAZ in lung fibroblasts may inhibit fibroblast proliferation and extracellular matrix deposition, while activating YAP/TAZ in alveolar epithelial cells may promote alveolar regeneration. In this review, we explore, for the first time, the bidirectional and cell-specific regulation of the Hippo/YAP pathway in IPF pathogenesis and discuss recent research progress and future prospects of IPF treatment based on Hippo/YAP signalling, thus providing a basis for the development of new therapeutic strategies to alleviate or even reverse IPF.
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