Histone deacetylase 3 promotes alveolar epithelial-mesenchymal transition and fibroblast migration under hypoxic conditionsopen access
- Authors
- Jeong, Sung Hwan; Son, Eun Suk; Lee, Young Eun; Kyung, Sun Young; Park, Jeong-Woong; Kim, Se-Hee
- Issue Date
- Jul-2022
- Publisher
- Springer Nature
- Citation
- Experimental and Molecular Medicine, v.54, no.7, pp.922 - 931
- Journal Title
- Experimental and Molecular Medicine
- Volume
- 54
- Number
- 7
- Start Page
- 922
- End Page
- 931
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/85287
- DOI
- 10.1038/s12276-022-00796-y
- ISSN
- 1226-3613
- Abstract
- Epithelial–mesenchymal transition (EMT), a process by which epithelial cells undergo a phenotypic conversion that leads to myofibroblast formation, plays a crucial role in the progression of idiopathic pulmonary fibrosis (IPF). Recently, it was revealed that hypoxia promotes alveolar EMT and that histone deacetylases (HDACs) are abnormally overexpressed in the lung tissues of IPF patients. In this study, we showed that HDAC3 regulated alveolar EMT markers via the AKT pathway during hypoxia and that inhibition of HDAC3 expression by small interfering RNA (siRNA) decreased the migration ability and invasiveness of diseased human lung fibroblasts. Furthermore, we found that HDAC3 enhanced the migratory and invasive properties of fibroblasts by positively affecting the EMT process, which in turn was affected by the increased and decreased levels of microRNA (miR)-224 and Forkhead Box A1 (FOXA1), respectively. Lastly, we found this mechanism to be valid in an in vivo system; HDAC3 siRNA administration inhibited bleomycin-induced pulmonary fibrosis in mice. Thus, it is reasonable to suggest that HDAC3 may accelerate pulmonary fibrosis progression under hypoxic conditions by enhancing EMT in alveolar cells through the regulation of miR-224 and FOXA1. This entire process, we believe, offers a novel therapeutic approach for pulmonary fibrosis. © 2022, The Author(s).
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