title: miR-21 promotes keratinocyte migration and re-epithelialization during wound healing.
abstract: 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.
authors.affiliation: Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Shui-Long
authors.initials: SL
authors.lastname: Guo
authors.forename: Kai-Ji
authors.initials: KJ
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: You-Liang
authors.initials: YL
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
mesh_terms: D015152:Blotting, Northern; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D016212:Transforming Growth Factor beta