Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
Int J Biol Sci. 2011;7(5):685-90. doi: 10.7150/ijbs.7.685. Epub 2011 May 30.
MicroRNAs involved in keratinocyte migration and wound healing are largely unknown. Here, we revealed the indispensable role of miR-21 in keratinocyte migration and in re-epithelialization during wound healing in mice. In HaCaT cell, miR-21 could be upregulated by TGF-β1. Similar to the effect of TGF-β1, miR-21 overexpression promoted keratinocyte migration. Conversely, miR-21 knockdown attenuated TGF-β1-induced keratinocyte migration, suggesting that miR-21 was essential for TGF-β-driven keratinocyte migration. Furthermore, we found that miR-21 was upregulated during wound healing, coincident with the temporal expression pattern of TGF-β1. Consistently, knockdown of endogenous miR-21 using a specific antagomir dramatically delayed re-epithelialization possibly due to the reduced keratinocyte migration. TIMP3 and TIAM1, direct targets of miR-21, were verified to be regulated by miR-21 in vitro and in vivo, indicating that these two molecules might contribute to miR-21-induced keratinocyte migration. Taken together, our results demonstrate that miR-21 promotes keratinocyte migration and boosts re-epithelialization during skin wound healing.
参与角质形成细胞迁移和伤口愈合的 microRNAs 很大程度上是未知的。在这里，我们揭示了 miR-21 在角质形成细胞迁移和小鼠伤口愈合中的再上皮化过程中的不可或缺的作用。在 HaCaT 细胞中，miR-21 可被 TGF-β1 上调。与 TGF-β1 的作用相似，miR-21 的过表达促进了角质形成细胞的迁移。相反，miR-21 的敲低减弱了 TGF-β1 诱导的角质形成细胞迁移，表明 miR-21 是 TGF-β 驱动角质形成细胞迁移所必需的。此外，我们发现 miR-21 在伤口愈合过程中上调，与 TGF-β1 的时间表达模式一致。一致地，使用特异性反义寡核苷酸敲低内源性 miR-21 会显著延迟再上皮化，可能是由于角质形成细胞迁移减少所致。TIMP3 和 TIAM1 是 miR-21 的直接靶标，在体外和体内均证实受 miR-21 调节，表明这两个分子可能有助于 miR-21 诱导的角质形成细胞迁移。总之，我们的研究结果表明，miR-21 促进角质形成细胞迁移，并在皮肤伤口愈合过程中促进再上皮化。
