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.

Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice

“…Initial assays were therefore conducted to evaluate if the therapeutic effects of exosomes from stimulated fibrocytes could be ascribed to their contents of proteins and miRs potentially capable of improving at least some of these alterations, on the basis of previous analyses [20,22,23,25,38,[44][45][46][47][48].…”

“…MiR-21 increases collagen release from fibroblasts, enhances the deposition of mature collagen fibrils in the wounds and promotes wound contraction at an early stage of the wound healing process [48]. It may also favor the re-epithelialization by directly enhancing keratinocyte proliferation [47] or indirectly, by increasing wound contraction [48]. MiR-126, miR-130a, and miR-132 are proangiogenic miRs that are induced by vascular endothelial growth factor and FGF-2 during normal wound healing and amplify the signaling cascade through multiple mechanisms [45].…”

Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

“…MiR-21 is also upregulated during the wound contraction and collagen deposition phases of skin wound healing [48], and promotes keratinocyte migration by inhibiting TIMP-3 [52]. MiR-21 is rapidly induced by TGF-β1 treatment, suggesting that it may be involved in the pro-fibrotic effects of TGF-β1 [5].…”

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

“…Inhibit proliferation and migration miR-182 [54]; let-7 [55]; miR-1 [56] Promote proliferation and migration miR-221, miR-222 [57] Cell type and function ncRNAs Inhibit migration miR-9 [58] Promote migration miR-132 [59] Regulate dedifferentiation and proliferation miR-34a [60] Regulate myelination miR-140 [60]; miR-29a [61] Regulate fibrinolysis miR-340 [ [83][84][85][86] miR-27b, miR-224 [87]; miR-574-3p, miR-31 [88] Inhibit proliferation miR-34, siRNA-P63 [89]; miR-720 [90]; miR-210, siRNA-E 2 F 3 [91] Improve proliferation, reduce differentiation miR-125b, siRNA-FGFR 2 [92,93] Inhibit proliferation, induce differentiation miR-24, siRNA-PAK4 [94] Keratinocytes Improve migration miR-205 [95][96][97] Inhibit migration, improve proliferation miR-483-3p [98] Inhibit migration miR-198 [99] Improve migration, inhibit migration miR-21 [100,101] Improve migration and proliferation miR-31, siRNA-EMP-1, siRNA-TGF-β [102] Regulate apoptosis lncRNA-p21 [103] Fibroblasts Inhibit proliferation let-7, miR-125 [104] Improve proliferation miR-29 [104]; miR-21 [105]; miR-22 [106]; lncRNA-H19 [107] Induce senescence miR-152, miR-181a [108]; miR-141 [109]; miR-143 [110]; miR-519a [11...…”

“…Of these, miR-210, miR-376a, miR-486-5p, miR-494, and miR-542-5p can enhance DNA damage and promote senescence. miR-21 was found to regulate fibroblast migration, which is critical to the success of skin tissue engineering [100,101].…”