期刊
MOLECULAR MEDICINE
卷 27, 期 1, 页码 -出版社
SPRINGER
DOI: 10.1186/s10020-021-00283-6
关键词
C/EBP beta; Fibrosis; Collagen; alpha-SMA; Pulmonary
资金
- National Natural Science Foundation of China [81500049]
- Social Development project of Jiangsu Province, China [BE2018631]
The study confirmed that deacetylation of C/EBP beta in A549 cells successfully ameliorated TGF-beta 1-induced EMT, as shown by reduction in alpha-SMA expression and excessive collagen-I accumulation. This indicates that the EMT and fibrotic effect of TGF-beta 1 depend on acetylated C/EBP beta-mediated regulation of alpha-SMA gene activity.
Background: Although the morbidity and mortality rates associated with idiopathic pulmonary fibrosis (IPF) are high, there is still lack of powerful and precise therapeutic options for IPF. Objec: Through in vitro model, this study sought to determine whether binding of acetylated CCAAT/enhancer binding protein beta (C/EBP beta) to alpha-smooth muscle actin (alpha-SMA) promoter could affect the activity of the latter as well as assess if it is essential for epithelial-to-mesenchymal transition (EMT) and extracellular matrix deposition in IPF. Methods: The expression of EMT and C/EBP beta in A549 cells treated with transforming growth factor-beta (TGF-beta) as pulmonary fibrotic model was detected by western blotting and qPCR. Collagen-I expression using ELISA was performed. The luciferase activity was used to examine the activity of C/EBP beta. Knockdown of C/EBP beta was performed by siRNA. We also investigated the effect of deacetylation of C/EBP beta on EMT using sirtuin 1 (SIRT1). The binding ability of C/EBP beta with alpha-SMA promoter was affirmed via chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assay (EMSA). The relationship between alpha-SMA and acetylated C/EBP beta was determined with co-immunoprecipitation (Co-IP). SiRNA-mediated knockdown of C/EBP beta in A549 cells attenuated TGF-beta 1-induced myofibroblast differentiation and ECM deposition. The extent of association between acetylated C/EBP beta and alpha-SMA promoter was dynamically monitored. Results: It was confirmed that deacetylation of C/EBP beta in A549 cells successfully ameliorated TGF-beta 1-induced EMT, as shown by reduction in alpha-SMA expression and excessive collagen-I accumulation. Conclusion: The EMT and fibrotic effect of TGF-beta 1 is dependent on acetylated C/EBP beta-mediated regulation of alpha-SMA gene activity. Thus, C/EBP beta acetylation may play a central role in pulmonary fibrosis.
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