Highlights d S1P is released from lung endothelial cells upon Pseudomonas aeruginosa injury d Angiocrine S1P promotes alveolar type II to type I cell transition d S1P regulates type II cell progenitor functions via a S1PR2-YAP signaling axis

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BackgroundIslet cell transplantation is one of the key treatments for type 1 diabetes. Understanding the mechanisms of insulin fusion and exocytosis are of utmost importance for the improvement of the current islet cell transplantation and treatment of diabetes. These phenomena have not been fully evaluated due either to the lack of proper dynamic imaging, or the lack of proper cell preservation during imaging at nanoscales.MethodsBy maintaining the native environment of pancreatic β-cells between two graphene monolayer sheets, we were able to monitor the subcellular events using in situ graphene liquid cell (GLC)-transmission electron microscopy (TEM) with both high temporal and high spatial resolution.ResultsFor the first time, the nucleation and growth of insulin particles until the later stages of fusion were imaged at nanometer scales. The release of insulin from plasma membrane involves the degradation of plasma membrane and drastic reductions in the shorter axis of the insulin particles. Sequential exocytosis results indicated the nucleation, growth and attachment of the new insulin particles to the already anchored ones, which is thermodynamically favorable due to the reduction in total surface, further reducing the Gibbs free energy. The retraction of the already anchored insulin toward the cell is also monitored for the first time live at nanoscale resolution.ConclusionInvestigation of insulin granule dynamics in β-cells can be investigated via GLC-TEM. Our findings with this technology open new realms for the development of novel drugs on pathological pancreatic β-cells, because this approach facilitates observing the effects of the stimuli on the live cells and insulin granules.

Alveoli are the functional units of blood-gas exchange in the lung and thus are constantly exposed to outside environments and frequently encounter pathogens, particles and other harmful substances. For example, the alveolar epithelium is one of the primary targets of the SARS-CoV-2 virus that causes COVID-19 lung disease. Therefore, it is essential to understand the cellular and molecular mechanisms by which the integrity of alveoli epithelial barrier is maintained. Alveolar epithelium comprises two cell types: alveolar type I cells (AT1) and alveolar type II cells (AT2). AT2s have been shown to function as tissue stem cells that repair the injured alveoli epithelium. Recent studies indicate that AT1s and subgroups of proximal airway epithelial cells can also participate alveolar repair process through their intrinsic plasticity. This review discussed the potential mechanisms that drive the reparative behaviors of AT2, AT1 and some proximal cells in responses to injury and how an abnormal repair contributes to some pathological conditions.

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