TGF-β-induced α-SMA expression is mediated by C/EBPβ acetylation in human alveolar epithelial cells

• Principais autores: Hui Ding (Autor), Jinjun Chen (Autor), Jingping Qin (Autor), Ruhua Chen (Autor), Zili Yi (Autor)
• Formato: Livro
• Publicado em: BMC, 2021-03-01T00:00:00Z.
• Assuntos: article
• Acesso em linha: Connect to this object online.
• Notes: 10.1186/s10020-021-00283-6; 1076-1551; 1528-3658
• Keywords: C/EBPβ; Fibrosis; Collagen; α-SMA; Pulmonary; Therapeutics. Pharmacology; RM1-950; Biochemistry; QD415-436
• Source: Molecular Medicine, Vol 27, Iss 1, Pp 1-12 (2021)

Abstract 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. Object Through in vitro model, this study sought to determine whether binding of acetylated CCAAT/enhancer binding protein β (C/EBPβ) to alpha-smooth muscle actin (α-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/EBPβ in A549 cells treated with transforming growth factor-beta (TGF-β) 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/EBPβ. Knockdown of C/EBPβ was performed by siRNA. We also investigated the effect of deacetylation of C/EBPβ on EMT using sirtuin 1 (SIRT1). The binding ability of C/EBPβ with α-SMA promoter was affirmed via chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assay (EMSA). The relationship between α-SMA and acetylated C/EBPβ was determined with co-immunoprecipitation (Co-IP). SiRNA-mediated knockdown of C/EBPβ in A549 cells attenuated TGF-β1-induced myofibroblast differentiation and ECM deposition. The extent of association between acetylated C/EBPβ and α-SMA promoter was dynamically monitored. Results It was confirmed that deacetylation of C/EBPβ in A549 cells successfully ameliorated TGF-β1-induced EMT, as shown by reduction in α-SMA expression and excessive collagen-I accumulation. Conclusion The EMT and fibrotic effect of TGF-β1 is dependent on acetylated C/EBPβ-mediated regulation of α-SMA gene activity. Thus, C/EBPβ acetylation may play a central role in pulmonary fibrosis.