Stress Dysregulates Genes Involved In Inflammation & Proliferation During Wound Healing Via MiR-155

Stress impairs wound healing by causing dysregulation of gene expression.  MicroRNAs are non-coding RNAs that can silence gene expression at the posttranscriptional level by binding to specific non-coding regions of target mRNAs.  We hypothesize that stress dysregulates miR-155 during the inflammation phase of wound healing resulting in altered gene expression of target genes.  Restraint stressed and control SKH1 (hairless) mice were wounded by 3.5mm punch biopsy on the dorsal part of the body.  Tissue was harvested day 0, day 1, & day 5.  Using qRT-PCR, the mRNA level of target genes was determined and analyzed by SPSS.  MiR-155 levels were upregulated in stressed mice.  Increased miR-155 would be expected to decrease the expression on specific inflammation target genes: SOCS1, TGFB1, IKBK, and IL13Ra.  The data shows a significant decrease of IKBK at day 0 (p = 0.009), SOCS1 at Day 1 (p = 0.001), and near significant decrease of TGFB1 at day 1 (p = 0.073).  Thus, modulating miR-155 could be a potential therapeutic approach to ameliorate stress impaired healing. Since stress has been shown to delay healing 27 - 40% in human and animal models, this has important clinical implications. Supported by NIH/NIDCR R01 DE017686 and Summer Research Opportunities Program, University of Illinois at Chicago.