Year: 2024
Type: article
Abstract: Objectives: To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on lung fibroblast activation and to examine the role of p66Shc in this process. Methods: An in vitro pulmonary fibrosis model was established using transforming growth factor-β (TGF-β)-induced MRC-5 lung fibroblasts. The proliferation and migration capacities of MRC-5 cells, along with the expression of fibrosis-related genes, were assessed following treatment with SAHA and/or silence of p66Shc. Results: In TGF-β-induced MRC-5 lung fibroblasts, SAHA treatment significantly inhibited cell proliferation and migration, as well as the expression of fibrosis-related genes, including collagen I and α-smooth muscle actin (SMA). Western blot and immunofluorescence assays revealed that SAHA increased p66Shc expression in both whole cells and mitochondria. Additionally, mito-SOX assay confirmed that SAHA treatment led to a marked accumulation of mitochondrial reactive oxygen species (ROS). However, silencing of p66Shc significantly reversed the aforementioned effects of SAHA on MRC-5 cells. Furthermore, chromatin immunoprecipitation (ChIP) assays demonstrated that SAHA enhanced active histone markers, H3K9Ac and H3K4Me3, in the p66Shc gene region. Conclusions: SAHA alleviates lung fibroblast activation and migration by increasing p66Shc expression and mitochondrial ROS generation through epigenetic modifications of histone 3.
Source: Aging Medicine
DOI: 10.1002/agm2.12385
Authors: Yiheng Dong, Jieting Peng, Xiangyu Zhang, Qiong Wang, Xing Lyu
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid:
Funder: National Science Foundation
Award: G3456337731
OpenAlex ID: W4405346799