ABSTRACT
AIM: To observe the effect and possible mechanism of stimulation of Yes-associated protein (YAP) activity on acute lung injury and repair induced by LPS in mice. METHODS: Ninety adult male ICR mice were divided into two groups: acute lung injury model group induced by LPS (7.5 mg/kg, i.p.) and LPS+XMU treatment (1 mg•kg-1•d-1) group. At 0 h, 24 h, 48 h and 72 h after LPS injection, the contents of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were detected by ELISA method. The activity of myeloperoxidase (MPO) and the content of protein in BALF were evaluated by chemical technique. The protein level of nuclear YAP, cytosol phosphorylated YAP (P-YAP), connective tissue growth factor (CTGF) and proliferating cell nuclear antigen (PCNA) in lung were analyzed by Western blot. RESULTS:The protein level of nuclear YAP at 24 h, 48 h and 72 h in lung of LPS+XMU group were up-regulated than those of LPS group by 39.2%, 148.1% and 42.9%, and the protein level of CTGF in lung were up-regulated than those of LPS group by 186.6%, 10.1% and 146.1% (P<0.05), respectively, while the protein level of cytosol P-YAP was down-regulated. The content of IL-6 and TNF-α at 24 h in BALF of LPS+XMU group were lower than those of LPS group by 28.4% and 23.7%, and the activity of MPO and the content of TNF-α at 48 h in BALF were lower by 13.5% and 39.5%, and the content of IL-6 and TNF-α at 72 h in BALF were lower by 42.8% and 16.7% (P<0.05), respectively. The protein level of PCNA at 48 h and 72 h in lung of LPS+XMU group were up-regulated than those of LPS group by 44.2% and 14.9% (P<0.05), respectively, while there was no significant difference at 24 h. The content of protein at 24 h, 48 h and 72 h in BALF of LPS+XMU group were lower than those of LPS group by 32.4%, 46.0% and 26.3% (P<0.05), respectively. The pathological changes showed a significantly attenuated tissue injury and accelerated recovery from lung injury in LPS+XMU group compared with mice injected with LPS alone at each times point. CONCLUSION: Stimulation of YAP activity attenuates lung injury and promotes lung recovery by alleviating lung inflammation and injury at injury phase, but by promoting inflammation resolution and stimulating cell proliferation at repair phase.