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- W2938604089 abstract "Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced cutaneous reactions, with keratinocyte apoptosis characterized to be the primary histologic feature. Exosomes are nanometre-sized vesicles with a lipid bilayer membrane and present in body fluids. They contain functional proteins, mRNAs, and miRNAs, induce immune dysfunction, and influence disease progress. Nevertheless, the potential roles of plasma exosomes and the underlying mechanisms in the context of SJS/TEN have yet to be explored. In our study, we firstly characterized exosomes isolated from plasma of SJS/TEN patients by transmission electron microscopy, nanoparticle tracking analysis, and western blot. These exosomes showed the expected size between 30 and 150 nm and showed positive staining for exosomal markers CD9, CD81 and TSG101. Deep sequencing analysis and qRT-PCR demonstrated that miR-375-3p was markedly upregulated in 35 SJS/TEN patients and positively correlated with clinical severity. Plasma exosomes were internalized by human primary keratinocytes and promoted their apoptosis. The miR-375-3p downregulated the X-linked inhibitor of apoptosis protein (XIAP), a key apoptosis regulator. Overexpressing XIAP attenuated miR-375-3p mediated keratinocyte apoptosis. Upregulating miR-375-3p repressed XIAP, mediated intrinsic keratinocyte apoptosis, and promoted mitochondrial membrane potential collapse, cytochrome c release, and Mfn-2 degradation. Our study is the first to show that circulating exosomal miR-375-3p enters keratinocytes, downregulates XIAP, induces intrinsic keratinocyte apoptosis via a mitochondrial pathway in SJS/TEN patients. Circulating exosomal miR-375-3p might be used as a potential disease marker for the diagnosis of SJS/TEN." @default.
- W2938604089 created "2019-04-25" @default.
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- W2938604089 date "2019-05-01" @default.
- W2938604089 modified "2023-09-30" @default.
- W2938604089 title "702 Plasma exosomal miR-375-3p regulates mitochondria-dependent keratinocyte apoptosis by targeting XIAP in SJS/TEN" @default.
- W2938604089 doi "https://doi.org/10.1016/j.jid.2019.03.778" @default.
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