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Exosomes derived from miR-16-5p-overexpressing keratinocytes attenuates bleomycin-induced skin fibrosis

microRNAs have been shown to be associated with the development of skin fibrosis. Therefore, miRNA modulators play an important role in the management of cutaneous fibrotic diseases and are worthy of investigation. However, a major obstacle of miRNAs therapy is to deliver miRNAs to target cell types, tissues or organs. The study reported here investigated the effects of miR-16-5p delivery by keratinocytes-derived exosomes on skin fibrosis in the bleomycin (BLM)-treated mice. In results, miR-16-5p-overexpressing keratinocytes-derived exosomes significantly suppressed the enhancing effects of TGF-β1 on proliferation, migration and COL1A1 expression of fibroblasts. Moreover, we found that miR-16-5p-overexpressing keratinocytes-derived exosomes inhibited the endogenous Smad3 expression. In vivo, subcutaneously injected of miR-16-5p-overexpressing keratinocytes-derived exosomes significantly enhanced miR-16-5p expression in the skin compared with the control group, while suppressing BLM-induced skin fibrosis with reduced dermal thickening and lower COL1A1 expression. In conclusion, our results suggest that the localized delivery of miR-16-5p by keratinocytes-derived exosomes may have potential for efficient clinical treatment of skin fibrosis.

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