Downregulation of let-7b promotes COL1A1 and COL1A2 expression in dermis and skin fibroblasts during heat wound repair

Abstract

MicroRNAs (miRs), a class of non-coding RNAs 18-25 nucleotides in length, generally serve suppressive role in the regulation of gene expression via directly binding to the 3'-untranslated region (UTR) of their target mRNA. Previous studies have identified several miRs to be involved in thermal injury repair. However, the role of miR let-7b during the recovery of thermal injury, in addition to the underlying mechanisms, has not previously been studied. In the present study, the expression of let-7b was observed to be significantly increased in skin tissue shortly following thermal injury, however, gradually reduced during the recovery of thermal injury. Notably, similar findings were observed in heat-denatured skin fibroblasts. Furthermore, collagen, type I, alpha 1 (COL1A1) and collagen, type I, alpha 2 (COL1A2), which are associated with the synthesis of type I collagen, were identified as two targets of let-7b in skin fibroblasts. The overexpression of let-7b was observed to upregulate the protein expression levels of COL1A1 and COL1A2, while knockdown of let-7b reduced the levels of COL1A1 and COL1A2 in skin fibroblasts. Furthermore, COL1A1 and COL1A2 were significantly downregulated shortly following thermal injury, while gradually upregulated during healing, in heat-damaged skin tissue and skin fibroblasts, with the expression profiles opposite to that of let-7b. Taken together, this suggests that the downregulation of let-7b in heat-damaged dermis promotes the synthesis of type I collagen and thus aids in burn wound repair.