(WHS-P53) ACCELERATION OF WOUND HEALING BY A GROWTH HORMONE RELEASING HORMONE AGONIST IN THE AGED MURINE MODEL
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
Background: The purpose of this study is to evaluate the in vivo effects of MR-409, an agonistic analog of growth hormone releasing hormone (GHRH), on wound healing in the aged murine model. Given the rapidly expanding elderly population globally, and the high mortality associated with chronic wounds in this population, effective and innovative approaches to wound healing are necessary. Our preliminary data revealed that MR-409 synthetic GHRH analogue fosters senescent fibroblast survival, proliferation, mobility, and collagen synthesis. To corroborate these in vitro findings and offer more clinically contextualized evidence of these effects, we tested the effect of GHRH agonist MR-409 on wound healing in the aged murine model.
Methods: Thirty 78-week-old male C57/BL6 mice were separated into three treatment groups; ten mice per group in each of three groups were subjected to 8 mm skin punch biopsies and the responses to topical application of 1 µg/day (low-dose) or 10 µg /day (high dose) of MR-409 were observed daily. Histologic analysis included aSMA staining, and photographs were taken on days 0, 4, 8 and 12.
Results: Results revealed enhanced wound healing with both low and high doses of MR-409 when compared to control group (p < 0.0001). The greatest differences appeared as early as day 4. Enhanced wound healing was supported by histologic analyses of the wounds which showed decreased fibrosis in treated groups as well as evidence of enhanced wound contraction necessary for wound closure.
Conclusion: These results suggest that MR-409 synthetic GHRH analogue accelerates wound healing in a dose-dependent manner on aged skin that otherwise exhibits delayed healing, likely through the differentiation of fibroblasts into contractile myofibroblasts that approximate the wound.