Exosomes derived from miR-16-5p-overexpressing keratinocytes attenuates bleomycin-induced skin fibrosis
Exosomes derived from miR-16-5p-overexpressing keratinocytes attenuates bleomycin-induced skin fibrosis
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源自 miR-16-5p 过表达角质形成细胞的外泌体可减轻博来霉素诱导的皮肤纤维化
DOI：
10.1016/j.bbrc.2021.05.046
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发表时间：
2021-05-19
影响因子：
3.1
通讯作者：
Yan, Yuan
中科院分区：
文献类型：
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作者：
Bo, Yunyao;Liu, Baiting;Yan, Yuan
microRNA已被证明与皮肤纤维化的发展有关。因此，miRNA调节剂在皮肤纤维化疾病的管理中发挥重要作用，值得研究。然而，miRNA治疗的主要障碍是将miRNA递送到靶细胞类型、组织或器官。本文报道的研究调查了角质形成细胞来源的外泌体递送miR-16- 5 p对博来霉素（BLM）治疗小鼠皮肤纤维化的影响。结果表明，过表达miR-16- 5的角质形成细胞来源的exosomes显著抑制TGF-01对成纤维细胞增殖、迁移和COL 1A 1表达的促进作用。此外，我们发现过表达miR-16- 5的角质形成细胞来源的exosomes抑制了内源性Smad 3的表达。在体内，与对照组相比，皮下注射过表达miR-16- 5 p的角质形成细胞来源的外泌体显著增强了皮肤中的miR-16- 5 p表达，同时抑制了BL诱导的皮肤纤维化，减少了真皮增厚和降低了COL 1A 1表达。总之，我们的研究结果表明，通过角质形成细胞来源的外泌体局部递送miR-16- 5 p可能具有有效临床治疗皮肤纤维化的潜力。
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-16-5poverexpressing keratinocytes-derived exosomes significantly suppressed the enhancing effects of TGF-01 on proliferation, migration and COL1A1 expression of fibroblasts. Moreover, we found that miR-16-5poverexpressing 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 BLMinduced 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.