Aim of the study
Acute lung injury (ALI) exhibits the features of noncardiogenic pulmonary edema and acute inflammatory process, and it also displays significant morbidity and mortality rates. This work focused on identifying how overexpression of PPARγ coactivator 1α (PGC-1α) positively regulated TFEB and mitophagy for resisting the lipopolysaccharide (LPS)-mediated ALI. Materials and
Conclusion
PGC-1α protects LPS-induced ALI by decreasing inflammation and alleviating lung edema. The mechanism might be positive regulation of TFEB directly and then upregulation of mitophagy in LPS-induced ALI.
Methods
The levels of autophagic proteins and inflammatory factors in LPS-induced ALI rats and primary type II alveolar epithelial cells were measured, respectively. Lung wet/dry ratios were calculated. Protein co-immunoprecipitation of PGC-1α and TFEB was detected. To explore the interaction between TFEB and PGC-1α, a luciferase reporter assay was conducted.
Results
The results showed that overexpression of PGC-1α decreases IL-1 and IL-6 but increases IL-10 in LPS-mediated ALI rats and type II alveolar epithelial cells (P < 0.05). Overexpression of PGC-1α can reduce lung edema in LPS-mediated ALI rats (P < 0.05). Overexpression of PGC-1α upregulates mitophagy-related proteins, such as TFEB, LC3B, Beclin, and LAMP1, and improves mitophagy in LPS-induced ALI. Protein immunoprecipitation indicated that TFEB and PGC-1α are interacting proteins. The luciferase reporter assay demonstrated that PGC-1α positively regulated TFEB in the LPS-induced primary type II alveolar epithelial cells.