Sirtuin 6 ameliorates bleomycin-induced pulmonary fibrosis via activation of lipid catabolism.
Jiangping HeCong YuYunlong ShenJiao HuangYanzi ZhouJianmin GuYing CaoQuan ZhengPublished in: Journal of cellular physiology (2023)
Pulmonary fibrosis is a chronic and serious interstitial lung disease with little effective therapies currently. Our incomplete understanding of its pathogenesis remains obstacles in therapeutic developments. Sirtuin 6 (SIRT6) has been shown to mitigate multiple organic fibrosis. However, the involvement of SIRT6-mediated metabolic regulation in pulmonary fibrosis remains unclear. Here, we demonstrated that SIRT6 was predominantly expressed in alveolar epithelial cells in human lung tissues by using a single-cell sequencing database. We showed that SIRT6 protected against bleomycin-induced injury of alveolar epithelial cells in vitro and pulmonary fibrosis of mice in vivo. High-throughput sequencing revealed enriched lipid catabolism in Sirt6 overexpressed lung tissues. Mechanismly, SIRT6 ameliorates bleomycin-induced ectopic lipotoxicity by enhancing lipid degradation, thereby increasing the energy supply and reducing the levels of lipid peroxides. Furthermore, we found that peroxisome proliferator-activated receptor α (PPARα) was essential for SIRT6-mediated lipid catabolism, anti-inflammatory responses, and antifibrotic signaling. Our data suggest that targeting SIRT6-PPARα-mediated lipid catabolism could be a potential therapeutic strategy for diseases complicated with pulmonary fibrosis.
Keyphrases
- pulmonary fibrosis
- oxidative stress
- ischemia reperfusion injury
- single cell
- fatty acid
- diabetic rats
- interstitial lung disease
- high glucose
- systemic sclerosis
- mouse model
- type diabetes
- gene expression
- drug induced
- rheumatoid arthritis
- high throughput sequencing
- emergency department
- rna seq
- adipose tissue
- metabolic syndrome
- drug delivery
- machine learning
- deep learning
- high throughput
- binding protein
- endothelial cells
- high fat diet induced