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

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 th...

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Veröffentlicht in:Journal of burn care & research 2021-11, Vol.42 (6), p.1266-1274
Hauptverfasser: Li, Qijie, Fang, Lu, Chen, Junjie, Zhou, Siqi, Zhou, Kai, Cheng, Fengrui, Cen, Ying, Qing, Yong, Wu, Junliang
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Sprache:eng
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Zusammenfassung: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.
ISSN:1559-047X
1559-0488
DOI:10.1093/jbcr/irab116