MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2
MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2
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MicroRNA Let-7b 通过靶向 IGF2BP2 抑制皮肤伤口愈合中的角质形成细胞迁移
DOI：
10.1111/exd.13164
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Yang, Xiao
中科院分区：
文献类型：
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作者：
Wu, Yan;Zhong, Julia Li;Yang, Xiao
创面愈合是一个复杂的过程，涉及角质形成细胞的增殖和迁移，以封闭表皮损伤。微RNA家族成员let-7b已在哺乳动物皮肤中表达，但其在角质形成细胞迁移中的确切作用尚不清楚。在这里，我们证明了let-7b通过靶向胰岛素样生长因子IGF2BP2来调节角质形成细胞的迁移。过表达let-7b导致HaCaT细胞迁移减少，而下调let-7b导致迁移增强。此外，在野生型小鼠的伤口愈合过程中，let-7b的表达降低，这使得我们构建了在皮肤中过表达let-7b的转基因小鼠。在创面愈合过程中，let-7b转基因小鼠表皮的再上皮化减少。利用生物信息学预测软件和报告基因分析，我们发现IGF2BP2是促进角质形成细胞迁移的let-7b的靶点。IGF2BP2表达载体的引入也挽救了let-7b诱导的迁移缺陷，证实了IGF2BP2是let-7b调控的重要靶点。我们的研究结果表明，let-7b显着延迟了再上皮化，可能是由于减少了角质形成细胞的迁移，并抑制了皮肤创面愈合过程中的IGF2BP2。
Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte-migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing.