Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across ...Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier.The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking.However,the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear.In the present study,deletion of GM130,which encodes for a matrix protein of the cis-Golgi cisternae,was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids.Specifically,the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum,Sftpb and Sftpc accumulation in the Golgi apparatus,and an increase in the compensatory secretion of Sftpd.Moreover,global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy;however,surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice.Therefore,our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.展开更多
基金supported by the National Natural Sciences Foundation of China(31730051 and 31601164)the National Key Research and Development Program of China(2018YFA0800900)+1 种基金Natural Science Foundation of Shandong Province,China(ZR2019PH076)the Open Project of Forensic Medicine Key Laboratory of Shanxi Province,China(SFM2019001)。
文摘Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier.The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking.However,the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear.In the present study,deletion of GM130,which encodes for a matrix protein of the cis-Golgi cisternae,was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids.Specifically,the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum,Sftpb and Sftpc accumulation in the Golgi apparatus,and an increase in the compensatory secretion of Sftpd.Moreover,global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy;however,surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice.Therefore,our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.
