SIRT6 attenuates LPS-induced inflammation and apoptosis of lung epithelial cells in acute lung injury through ACE2/STAT3/PIM1 signaling.

Abstract

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. 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. 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. SIRT6 eased LPS-evoked inflammation and apoptosis of lung epithelial cells in ALI through ACE2/STAT3/PIM1 signaling.