Bezafibrate attenuates acute lung injury by preserving mitochondrial dynamics equilibrium in pulmonary epithelial cells.

Acute lung injury (ALI) serves as a common life-threatening clinical syndrome with high mortality rates, which is characterized by disturbed mitochondrial dynamics in pulmonary epithelial barrier. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the critical nuclear receptors, exerting important roles in preserving mitochondrial dynamics equilibrium. Previous studies have suggested that bezafibrate (BEZ), a PPAR-γ agonist, could improve obesity and insulin resistance. In the present study, we explored whether bezafibrate could attenuate lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. Using C57BL/6 mice exposed to LPS, we observed that BEZ pretreatment (100 mg/kg) for 7 days decreased lung pathologic injury, reduced oxidative stress, suppressed inflammation and apoptosis, accompanied by shifting the dynamic course of mitochondria from fission into fusion. Meanwhile, we observed that BEZ could reverse the inhibition of PPAR-γ in lung tissues from LPS-treated mice. In vitro experiments also disclosed that BEZ could improve cell viability in primary pulmonary epithelial cells in a concentration-dependent manner. And BEZ (80 µM) treatment could not only inhibit oxidative stress but also preserve mitochondrial dynamics equilibrium in primary pulmonary epithelial cells. However, PPAR-γ knockdown partially abolished BEZ-mediated antioxidation and completely offset its regulatory effects on mitochondrial dynamics in primary pulmonary epithelial cells. In PPAR-γ-deficient mice, BEZ lost its pulmonary protection including anti-inflammatory and antioxidative effects in mice with ALI. Taken together, BEZ could attenuate ALI by preserving mitochondrial dynamics equilibrium in pulmonary epithelial cells in a PPAR-γ-dependent manner.