论文部分内容阅读
Recently, concerns about the inhalation risks of ultrafine particles (UFPs) have increased with the continued development of new nanotechnologies and air pollution.Limited evidences have shown UFP could induce pulmonary fibrosis, the corresponding mechanism is frequently contributed to ROS and inflammation.However, accumulating evidence indicated that the extent of alveolar epithelial cell (AEC) injury and lack of sufficient repair are critical determinants of pulmonary fibrosis.Whether and how UFP impairs AEC and induces pulmonary fibrosis remains elusive.Here, we showed that UFP induced autophagosome accumulation was accompanied by unchanged mTOR.Furthermore, we investigated the cellular and molecular mechanism of UFP-induced autophagy in AEC by focusing on autophagic flux.Autophagic flux inhibition which is proved by increasing p62 is due to decreased lysosomal degradative capacity rather than affecting autophagosome-lysosome fusion.Further morphological and functional analysis indicated that UFP significantly impaired lysosomal acidification leading to the decreased degradative capacity, the conclusion also is supported by rescuing lysosomai acidification could enhancing autophagic flux.Finally, rescuing lysosomal acidification might protect AEC from apoptosis, a key process of ACE in pulmonary fibrosis.These date suggested that UFP inhibited autophagic flux via targeting lysosomal acidification, and thus regulated apoptosis of AEC, and this may be critical to the development of pulmonary fibrosis associated with UFP.