Mechanism Of Osteopontin Mediated Autophagy In The Formation Of Hypoxic Pulmonary Hypertension In Mice

Objective To observe the effect of osteopontin(OPN)on the expression of autophagy-related proteins(Beclin-1 and LC3B)and signaling pathway proteins(p38MAPK,PI3 K,NF-κB)in the lung tissue of mice under hypoxia,and to explore the role and mechanism of osteopontin(OPN)-mediated autophagy in the formation of hypoxic pulmonary hypertension.Methods C57BL/6 mice were divided into: normoxia control group,normoxia combined with OPN-/-group,hypoxia control group,and hypoxia combined with OPN-/-group.The mean pulmonary arterial pressure(m PAP)and right ventricular hypertrophy index(RVHI)of the mice were measured by right heart intubation method.The morphological changes of lung tissue and pulmonary artery were observed.Western-blot method was used to detect the protein expression of Beclin-1,LC3 B,OPN,p38 MAPK,PI3K,and NF-κB in lung tissue of each group.RT-PCR method was used to examine the expression of Beclin-1,LC3 B,OPN,p38 MAPK,PI3K,and NF-κB m RNA in mouse lung tissue.The results were analyzed analytically.Result Compared with the normoxia group,the m PAP and RVHI of the hypoxia group were increased(P<0.05),and the expression levels of Beclin-1 and LC3 B in the lung tissue of the hypoxia group were increased(P<0.05).The expression levels of p38 MAPK,PI3K and NF-κB were also higher than those in the normoxia group(P<0.05);Under normoxic and hypoxic conditions,compared with the control group,the m PAP and RVHI of the OPN-/-group were decreased(P<0.05).The expression levels of Beclin-1 and LC3 B were increased(P<0.05),while the expression levels of p38 MAPK,PI3K and NF-κB were decreased(P<0.05).Conclusion Hypoxia can promote the expression of OPN and autophagy-related proteins in lung tissue.After knocking out OPN gene,the expression levels of autophagy-related proteins Beclin-1 and LC3 B were significantly increased,suggesting that OPN has an inhibitory effect on autophagy;m PAP and RVHI decreased,and the expression levels of p38 MAPK,PI3K,and NF-κB decreased,indicating that OPN may activate p38 MAPK,PI3K,NF-κB signaling pathway to regulate the formation of hypoxic pulmonary hypertension.