| Scleroderma,a complex autoimmune disease,is difficult to be cured by the large side effects of commonly used immunotherapeutic drugs.Mesenchymal stem cells(MSCs)have become a promising therapeutic approach due to their powerful immunomodulatory functions,and their derivative exosomes can act as carriers to transport microRNAs and other active ingredients to target cells for immunomodulation and repair of damage,and miRNAs may be the key mechanism for their function.In this study,the results showed that both reduced the skin thickness of the model mice,as well as macrophage inflammation infiltration at the site of the lesion by injecting umbilical cord-derived mesenchymal stem cells(UC-MSC)and their exosomes(exosomes,EXO)intravenously into a HOCl-induced mouse model of scleroderma.Exosomes can achieve anti-inflammatory and anti-fibrotic effects similar to MSCs.In vitro experiments have shown that UC-MSC-EXO can target LPS-induced THP-1,significantly inhibit the expression of pro-inflammatory M1 macrophage markers,promote the expression of anti-inflammatory M2 macrophage markers,make macrophages more polarized to M2,and significantly inhibit the activation of the TLR4/MYD88/NF-κB inflammatory pathway.The high-throughput sequencing results of UC-MSC and UC-MSC-EXO microRNAs suggested that UC-MSC-EXO enriched 266 miRNAs in umbilical cord mesenchymal stem cells,of which let-7 family members were abundant and let-7i were the most enriched.Under inflammatory or non-inflammatory conditions,let-7i overexpression can promote polarization of macrophages to M2,inhibit the TLR4/MYD88/NF-κB pathway,and exert anti-inflammatory effects.Transfection of let-7i inhibitors has the opposite effect.The conclusion of this study is that let-7i of UC-MSC-EXO can target macrophages,inhibit the inflammatory response through the TLR4/MYD88/NF-κB pathway,and produce therapeutic effects on scleroderma mice.Figures 22,Tables 25,References 88... |
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