Differential expression of microRNA let-7b-5p regulates burn-induced hyperglycemia

Abstract

One of the classical features observed in patients with burn injury is hyperglycemia. There have been previous reports that a cohort of microRNAs (miRNAs) is differentially expressed in the dermis of patients with burn injury. More specifically, it has been shown that the miR-194 can target the insulin-like growth factor receptor 1 (IGF1R) and silence its protein expression resulting in hyperglycemia. The objective of the current study was to discover if additional miRNA-mediated post-transcriptional mechanism exists that lead to suppression of IGF1R protein expression post-burn injury. Using the 30% total body surface area (TBSA) model of burn injury in rats we found that the miRNA let-7b can target IGF1R and downregulate its protein expression, in turn attenuating PI3K/Akt and Gsk3β activation leading to hyperglycemia. Increased let-7b expression was significantly more than the previously reported miR-194 both in the burn rats compared to sham and in patients with burn injury compared to healthy subjects. Serum from burn rats also resulted in decreased IGF1R protein expression in rat L6 myotubes. In vivo targeting of let-7b by antagomir mitigated the effect of increased let-7b expression on IGF1R protein expression and hyperglycemia. Thus targeting let-7b might be a promising approach to treat hyperglycemia in patients with burn injury.