Exosomal MicroRNA-21 Promotes Keloid Fibroblast Proliferation and Collagen Production by Inhibiting Smad7

瘢痕疙瘩 成纤维细胞 小RNA 伤口愈合 医学 癌症研究 细胞生物学 细胞培养 免疫学 生物 病理 基因 遗传学
作者
Qijie Li,Fang Lü,Junjie Chen,Siqi Zhou,Kai Zhou,Fengrui Cheng,Ying Cen,Yong Qing,Junliang Wu
出处
期刊:Journal of Burn Care & Research [Oxford University Press]
卷期号:42 (6): 1266-1274 被引量:17
标识
DOI:10.1093/jbcr/irab116
摘要

Abstract In keloid fibroblasts, microRNA-21 (miR-21) enhances activation of the TGF-β–Smad signaling pathway by down-regulating Smad7 expression, thereby promoting keloid fibroblast proliferation and collagen production. However, it is unclear whether miR-21 performs the above-mentioned functions through exosomal transport. Here, we extracted exosomes from the culture supernatants of keloid and normal skin fibroblasts and observed that both types of cells above secrete exosomes; however, keloid fibroblasts secreted significantly more exosomal miR-21 than normal skin fibroblasts (P < .001). Interestingly, we also observed that exosomal miR-21 could enter target keloid fibroblasts. In addition, inhibiting exosomal miR-21 up-regulated Smad7 protein expression and reduced Smad2 and Smad3 protein levels in target keloid fibroblasts. Furthermore, inhibiting exosomal miR-21 down-regulated collagen I and collagen III expression in target keloid fibroblasts, increased the proportion of apoptotic cells, and reduced cell proliferation. Taken together, these results show that exosomal miR-21 promoted proliferation and collagen production in keloid fibroblasts by inhibiting Smad7. Thus, we identified regulatory roles for miR-21 in promoting keloid fibroblast proliferation and participating in keloid formation and development. These findings imply that miR-21 may serve as a novel target for controlling the development of keloids.
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