Background
Acute lung injury (ALI) is a severe and fatal respiratory disease. SIRT6 exerts pivotal activities in the process of lung diseases, but whether SIRT6 impacts ALI has not been covered.
Conclusion
SIRT6 eased LPS-evoked inflammation and apoptosis of lung epithelial cells in ALI through ACE2/STAT3/PIM1 signaling.
Methods
Lentivirus recombinant expressing vector SIRT6 gene (Lent-SIRT6) was constructed in mice, and there were control, lipopolysaccharide (LPS), LPS + Vehicle, and LPS + Lent SIRT6 groups. RT-qPCR and western blot detected SIRT6 expression in lung tissues. HE staining observed pathological alternations in lung tissues. Wet-to-dry ratio of the lungs was then measured. The cell count of bronchoalveolar lavage fluid (BALF) was evaluated. Serum inflammation was examined with enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot were to measure apoptosis. Western blot tested the expression of ACE2/STAT3/PIM1 signaling-associated factors. At the cellular level, LPS was used to induce lung epithelial cells BEAS-2B to establish cell injury models. SIRT6 was overexpressed and ACE2 expression was inhibited by cell transfection, and the mechanism of SIRT6 in LPS-induced lung injury model was further explored by Cell Counting Kit-8 (CCK-8), western blot, quantitative reverse-transcription polymerase chain reaction, TUNEL, and other techniques.
Results
The results of animal experiments showed that SIRT6 overexpression could reduce LPS-induced lung pathological injury, pulmonary edema, and BALF cell ratio and attenuate LPS-induced inflammatory response and cell apoptosis. In the above process, ACE2, STAT3, p-STAT3, and PIM1 expression were affected. In cell experiments, SIRT6 expression was reduced in LPS-induced BEAS-2B cells. Inhibition of ACE2 expression could reverse the inhibitory effect of SIRT6 overexpression on ACE2/STAT3/PIM1 pathway, and cellular inflammatory response and apoptosis.