Bach1 Deficiency Ameliorates Radiation Pneumonitis via Activating TFAM Signaling Pathway.

Abstract

Aims: BTB and CNC homology 1 (Bach1) is a transcription factor that mediates oxidative stress and inflammation and participates in the progression of diseases such as atherosclerosis, colitis, and acute lung injury. In this study, we aimed to explore the role of Bach1 in radiation pneumonitis (RP) and elucidate its underlying mechanism. Results: Bach1 expression was significantly elevated in the lung tissues of RP mice. Deletion of the Bach1 gene markedly ameliorated X-ray-induced RP by reducing inflammation and oxidative stress. In vitro experiments demonstrated that Bach1 deficiency mitigated radiation-induced oxidative damage and inflammation in bone marrow-derived macrophages. Conversely, Bach1 overexpression exacerbated oxidative stress and inflammation in radiation-treated macrophages. Mechanistically, using the JASPAR database, electromobility shift assays, and luciferase reporter assays, we revealed that Bach1 inhibited mRNA expression of mitochondrial transcription factor A (TFAM) by directly binding to its promoter region. Innovation and Conclusion: Our findings indicate that silencing of Bach1 protects against RP by upregulating the mRNA expression of TFAM, which, in turn, enhances mitochondrial function and reduces inflammation and oxidative stress. This study provides valuable insights into potential therapeutic strategies for patients with RP through Bach1 inhibition. Antioxid. Redox Signal. 00, 000-000.