Zhang Yanming,Wu Wenjia,Meng Ting,Yang Shuiping,Miao Gong
This study aimed to investigate the role of miR-25-3p carried by human amnion epithelial cell (hAEC)–derived exosomes in regulating MUC5AC production and apoptosis in conjunctival goblet cells. hAEC-derived exosomes were isolated, characterized, and evaluated for their uptake by conjunctival goblet cells. qRT-PCR, flow cytometry, Western blotting, and ELISA were used to assess the effects of exosomes on MUC5AC expression and apoptosis, with a focus on the contribution of miR-25-3p. The interaction between miR-25-3p and its predicted target BCL2L11 was examined using dual-luciferase reporter assays. Conjunctival goblet cells efficiently internalized hAEC-derived exosomes. Exosome treatment increased MUC5AC expression ( P < 0.01) and reduced apoptosis ( P < 0.01). miR-25-3p was found to mediate these effects, at least in part, through targeting BCL2L11, thereby promoting MUC5AC production ( P < 0.01) and decreasing apoptosis ( P < 0.01). hAEC-derived exosomes, particularly those containing miR-25-3p, modulate mucin expression and apoptosis in conjunctival goblet cells. These findings provide mechanistic insight into how exosomal miRNAs may contribute to maintaining ocular surface homeostasis, suggesting a potential role for exosomal miR-25-3p in supporting ocular surface health.
Danting Wang,Xuedong Wang,Haishan Huang,Huili Wang
Herein, we demonstrated that triclosan (TCS) induced neurotoxicity mediated by pre-mRNA alternative splicing (AS). TCS exposure resulted in a series of phenotypic malformations, abnormal locomotor behavior, circadian rhythm disorder and inhibited AChE activity. High throughput mRNA sequencing revealed that TCS regulated the AS events of nerve-related genes. Meanwhile, abnormal expression was observed in marker genes related to nerve cell migration, axon guidance and myelination. The expression of mitochondrial apoptosis activator bcl2l11 was significantly increased under TCS exposure. Interestingly, CELF2 as one of the important RNA-binding proteins was closely related to the AS events, and its mRNA and protein expression levels were significantly increased in zebrafish brain under acute or chronic TCS exposure. Functional knock-down and over-expression of celf2 confirmed that TCS led to nervous system injury and developmental defects through the CELF2-mediated AS events of genes ( mbpa , mef2d , u2af2b and matn3b ). Histopathological injury, phenotypic malformation, abnormal locomotor behavior and changes in neuromarkers all confirmed the biological functions of CELF2 in zebrafish brain. These findings demonstrate that TCS might regulate some of the AS events of nerve-related genes through upregulating the expression of CELF2. Thus, CELF2 may serve as a target for the prevention, diagnosis and treatment of contaminant-induced neurological diseases.
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