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

Area of Science:

• Biochemistry
• Molecular Biology
• Endocrinology

Background:

• Hyperglycemia is a common complication following burn injury.
• MicroRNAs (miRNAs) are implicated in post-burn hyperglycemia, with miR-194 previously shown to target insulin-like growth factor receptor 1 (IGF1R).

Purpose of the Study:

• To investigate additional miRNA-mediated mechanisms regulating IGF1R protein expression and contributing to hyperglycemia after burn injury.
• To identify novel therapeutic targets for managing burn-related metabolic dysfunction.

Main Methods:

• Utilized a rat model with 30% total body surface area (TBSA) burn injury.
• Quantified miRNA expression levels and IGF1R protein in burn-injured rats and human patients.
• Assessed the effect of burn rat serum on IGF1R expression in L6 myotubes.
• Administered antagomir targeting let-7b in vivo to evaluate its impact on IGF1R and hyperglycemia.

Main Results:

• Identified let-7b as a miRNA that targets IGF1R, downregulating its protein expression and consequently attenuating PI3K/Akt and Gsk3β activation, leading to hyperglycemia.
• Observed significantly higher let-7b expression in burn-injured rats and patients compared to controls.
• Demonstrated that serum from burn rats reduced IGF1R protein expression in L6 myotubes.
• Showed that in vivo let-7b inhibition using antagomir reversed the effects on IGF1R protein expression and hyperglycemia.

Conclusions:

• let-7b is a key regulator of IGF1R post-transcriptional expression in the context of burn injury-induced hyperglycemia.
• let-7b exhibits greater differential expression post-burn compared to miR-194.
• Targeting let-7b presents a potential therapeutic strategy for managing hyperglycemia in burn patients.