Background: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. Results: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (IECs) to investigate the communication between MCs and IECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into IECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. Conclusions: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.

The nervous system is one of the most complex and fascinating organ systems in the metazoan. Neural networks regulate many aspects of animal physiology and behavior. The longheld doctrine that neurons are only produced in the embryo 1,2 has been challenged by the discovery that neurogenesis persists in the central nervous system (CNS) of adult animals. 3 It is now accepted that adult neurogenesis is a widespread phenomenon in different metazoans. 4,5 As vertebrates, zebrafish have shown that adult neurogenesis is along the entire rostral-caudal axis of the brain 6 and when their CNS

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Lamins are the ancient type V intermediate filament proteins contributing to diverse biological functions, such as the maintenance of nuclear morphology, stabilization of chromatin architecture, regulation of cell cycle progression, regulation of spatial-temporal gene expressions, and transduction of mechano-signaling. Deregulation of lamins is associated with abnormal nuclear morphology and chromatin disorganization, leading to a variety of diseases such as laminopathy and premature aging, and might also play a role in cancer. Accumulating evidence indicates that lamins are functionally regulated by post-translational modifications (PTMs) including farnesylation, phosphorylation, acetylation, SUMOylation, methylation, ubiquitination, and O-GlcNAcylation that affect protein stabilization and the association with chromatin or associated proteins. The mechanisms by which these PTMs are modified and the relevant functionality become increasingly appreciated as understanding of these changes provides new insights into the molecular mechanisms underlying the laminopathies concerned and novel strategies for the management. In this review, we discussed a range of lamin PTMs and their roles in both physiological and pathological processes, as well as potential therapeutic strategies by targeting lamin PTMs.