The role of mast cells in cellular modifications evoked by Exendin-4 in treated wounds: a preclinical study

Abstract

Objective: To assess the response of cellular infiltration in wounds treated with Exendin-4. Method: In this study, 16 mice were used. On each mouse, two wounds were produced, one above the other, in order to study the effects of the various treatments carried out. The wounds then received an intradermal injection of either saline (20μl; Group 1) or Exendin-4 (Exe4, 62ng; Group 2) in the upper and lower wounds, respectively. The mice were euthanised in order to collect the wounds at time of abrasion (T0), at 48 hours (T1), 96 hours (T2) and 144 hours (T3). The expression of the glucagon-like peptide-1 receptor (GLP-1R) was evaluated by Western blot in wound lysates. Histological and histochemistry methods were applied in cryosections. Results: In T2 and T3 treated wounds, the mast cells degranulation index increased while GLP-1R expression, tumour necrosis factor (TNF)-α, or heat shock protein (HSP)47 antigens were detected in their cytoplasm. These cells interacted with dendritic cells, vessels or granulocytes. The density of dendritic cells increased progressively, and intercellular connections were found between these cells and vessels. Among the dendritic cells at T2, only M2 macrophages increased. However, M1 cells expressed transforming growth factor (TGF)-β and both interacted with either fibroblasts or with vessels. The number of plasmacytoid dendritic cells increased and established close contacts with regulatory T cells. Conclusion: We propose that after treatment with Exe4, early activation of mast cells is critical in wound healing acceleration. This is crucial in understanding the potential effect of this drug for viable clinical therapies.