miRNA-29 regulates epidermal and mesenchymal functions in skin repair

MicroRNAs (miRNAs) control organogenesis in mammals by inhibiting translation of mRNA. Skin is an excellent model to study the role of miRNAs in epidermis and the mesenchyme. Previous research demonstrated miRNA-29 family functions in skin; however, the mRNA targets and the downstream mechanisms of miRNA-29-mediated regulation are missing. We used the miRNA crosslinking and immunoprecipitation method to find direct targets of miRNA-29 in keratinocytes and fibroblasts from human skin. miRNA-29 inhibition using modified antisense oligonucleotides in 2D and 3D cultures of keratinocytes and fibroblasts enhanced cell-to-matrix adhesion through autocrine and paracrine mechanisms of miRNA-29-dependent tissue growth. We reveal a full transcriptome of human keratinocytes with enhanced adhesion to the matrix, which supports regeneration of the epidermis and is regulated by miRNA-29. Impact statement The functions of small, therapeutically targetable microRNA molecules identified in our study can provide a new approach to improve wound healing by restoring and enhancing the inner molecular mechanisms of a cell and its surrounding matrix. We also provide a plethora of new mRNA targets for follow-up studies of cell adhesion and extracellular matrix formation in humans.