MicroRNA Profiling in Mid- and Late-Gestational Fetal Skin: Implication for Scarless Wound Healing

Abstract

Mid-gestational mammalian skin has unique capacity to heal without scar. Fetal skin undergoes phenotypic transition from scarless healing to scar repairing during embryonic development. However, the molecular mechanisms underlying the scarless phenotype and phenotypic transition remain largely unknown. MicroRNAs (miRNAs) are a novel class of small regulatory RNAs emerged as post-transcriptional gene repressors and play essential roles in diverse pathophysiological processes including skin morphogenesis and pathogenesis. Here, we performed a genome-wide miRNA profiling to identify the differentially expressed miRNAs between mid-gestational (E16 day) and late-gestational (E19 day) mouse skin, corresponding to scarless and scarring phenotype, respectively. Two miRNAs (miR-29b and miR-29c) with highest fold changes were further validated independently by real-time RT-PCR. Functional annotations of putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that these predicted targets, including Smads, beta-catenin and Ras, were significantly enriched and involved in several signaling pathways important for scarless wound healing. In addition, Dicer, one of the key RNase III responsible for miRNA biogenesis and functions, was found to be up-regulated in the E19 fetal skin as compared with the E16 counterpart. Taken together, our results identified differentially expressed miRNAs between mid-and late-gestational fetal skin that correlated with phenotypic transition from scarless to scarring repair during skin development. Our bioinformatics' analysis suggests that miRNAs might contribute to this phenotypic transition probably by affecting multiple target genes and signaling pathways.