Department of Plastic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
J Cell Mol Med. 2022 Apr;26(8):2299-2311. doi: 10.1111/jcmm.17250. Epub 2022 Feb 24.
Proliferation and migration of keratinocytes are vital processes for the successful epithelization specifically after wounding. MiR-221 has been identified to play a potential role in promoting wound regeneration by inducing blood vessel formation. However, little is known about the role of miR-221 in the keratinocyte proliferation and migration during wound healing. An in vivo mice wound-healing model was generated; the expression levels of miR-221 were assessed by qRT-PCR and fluorescence in situ hybridization. Initially, we found that miR-221 was upregulated in the proliferative phase of wound healing. Further, in an in vivo wound-healing mice model, targeted delivery of miR-221 mimics accelerated wound healing. Contrastingly, inhibition of miR-221 delayed healing. Additionally, we observed that overexpression of miR-221 promoted cell proliferation and migration, while inhibition of miR-221 had the opposite effects. Moreover, we identified SOCS7 as a direct target of miR-221 in keratinocytes and overexpression of SOCS7 reversed the effects of miR-221 in HaCaT keratinocytes. Finally, we identified that YB-1 regulates the expression of miR-221 in HaCaT keratinocytes. Overall, our experiments suggest that miR-221 is regulated by YB-1 in HaCaT keratinocytes and acts on SOCS7, thereby playing an important role in HaCaT keratinocyte proliferation and migration during wound healing.
角质形成细胞的增殖和迁移是成功上皮化的关键过程,特别是在创伤后。miR-221 已被确定通过诱导血管形成在促进伤口再生中发挥潜在作用。然而,miR-221 在伤口愈合过程中角质形成细胞增殖和迁移中的作用知之甚少。建立了体内小鼠伤口愈合模型;通过 qRT-PCR 和荧光原位杂交评估 miR-221 的表达水平。最初,我们发现 miR-221 在伤口愈合的增殖期上调。此外,在体内伤口愈合小鼠模型中,miR-221 模拟物的靶向递送加速了伤口愈合。相反,抑制 miR-221 会延迟愈合。此外,我们观察到过表达 miR-221 促进细胞增殖和迁移,而抑制 miR-221 则产生相反的效果。此外,我们鉴定出 SOCS7 是角质形成细胞中 miR-221 的直接靶标,SOCS7 的过表达逆转了 miR-221 在 HaCaT 角质形成细胞中的作用。最后,我们确定 YB-1 调节 HaCaT 角质形成细胞中 miR-221 的表达。总之,我们的实验表明,miR-221 在 HaCaT 角质形成细胞中受 YB-1 调控,并作用于 SOCS7,从而在伤口愈合过程中角质形成细胞增殖和迁移中发挥重要作用。