The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice

Abstract

Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice.

Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in Diabetic Mice

“…We found few MCs in inflamed skin wounds (Figure 4(a)), but MCs began to increase rapidly during the remodeling phase. This finding is consistent with a report by Nishikori et al [30]. Additionally, in our experiment, MCs were significantly decreased after sympathectomy (Figure 4(b)).…”

Mast Cells Regulate Wound Healing in Diabetes

“…Of note, none of these studies used diabetic mice. The only study that aimed at evaluating the role of MCs in STZ-induced diabetic mice failed to observe a solid difference in wound closure between diabetic and nondiabetic mice, but demonstrated differences in wound neovascularization and MC accumulation postinjury, suggesting that MCs participate in wound healing ( 43 ). Finally, and most importantly, none of the above-mentioned studies have used MC degranulation inhibitors in diabetic mice to provide results comparable to the ones reported here.…”

Hydroethanolic Extract of Strychnos pseudoquina Accelerates Skin Wound Healing by Modulating the Oxidative Status and Microstructural Reorganization of Scar Tissue in Experimental Type I Diabetes

“…Romero-Cerecero et al [ 68 ] demonstrated that the topical use of medicinal plants such as Ageratina pichinchensis in wound healing in diabetic rats stimulates an increase of cellularity and vascularity in the injured tissue. In addition to phagocytes and fibroblasts, mast cells are also found in abundance during the tissue repair process and play an important role in the production of angiogenic factors such as VEGF and TGF- β 1, exerting a great influence on the proliferative response in the healing of cutaneous wounds [ 69 ]. In the present study, a dose-response increase in the mast cells number in groups treated with S. pseudoquina extract was observed.…”