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    Regulation of MMP 2 and MMP 9 expressions modulated by AP-1 (c-jun) in wound healing: improving role of Lucilia sericata in diabetic rats
    (Springer-Verlag Italia Srl, 2019) Tombultürk, Fatma Kübra; Soydaş, Tuğba; Saraç, Elif Yaprak; Tunçdemir, Matem; Coşkunpınar, Ender; Polat, Erdal; Sirekbasan, Serhat; Kanigur-Sultuybek, Gönül
    AimsLucilia sericata larvae have been successfully used on healing of wounds in the diabetics. However, the involvement of the extraction/secretion (ES) products of larvae in the treatment of diabetic wounds is still unknown. Activator protein-1 (AP-1) transcription, composed of c-jun and c-Fos proteins, has been shown to be the principal regulator of multiple MMP transcriptions under a variety of conditions, also in diabetic wounds. Specifically, MMP-2 and MMP-9's transcriptions are known to be modulated by AP-1. c-jun has been demonstrated to be a repressor of p53 in immortalized fibroblasts. The aim of the present study is to investigate the effects of L. sericata ES on the expression of AP-1 (c-jun), p53, MMP-2, and MMP-9 in wound biopsies dissected from streptozotocin induced diabetic rats.MethodsThe expression levels of MMP-2, MMP-9, c-jun and p53 in dermal tissues were determined at days 0, 3, 7 and 14 after wounding, using immunohistochemical analysis and quantitative real-time PCR.ResultsThe treatment with ES significantly decreased through inflammation-based induction of MMP-2 and MMP-9 expression levels in the wounds of diabetic groups, compared to control groups at the third day of wound healing. At the 14th day, there were dramatic decreases in expression of c-jun, MMP-9, and p53 in ES-treated groups, compared to the diabetic group (P<0.001, P<0.05 and P<0.01, respectively).ConclusionES products of L. sericata may enhance the process of wound healing in phases of inflammation, proliferation, and re-epithelization, essentially via regulating c-jun expression and modulating MMP-2 and MMP-9 expressions.
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    Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats
    (Springer Link, 2021) Tombultürk, Fatma Kübra; Todurga-Seven, Zeynep Gizem; Hüseyinbaş, Önder; Özyazgan, Sibel; Turgut, Ulutin; Kanigur-Sultuybek, Gönül
    Background: Diabetic chronic wound, which is one of the diabetic complications caused by hyperglycemia, characterized by prolonged inflammation has become one of the most serious challenges in the clinic. Hyperglycemia during diabetes not only causes prolonged inflammation and delayed wound healing but also modulates the activation of nuclear factor-kappa B (NF-?B) and the expression of matrix metalloproteinases (MMPs). Although metformin is the oldest oral antihyperglycemic drug commonly used for treating type 2 diabetes, few studies have explored the molecular mechanism of its topical effect on wound healing. Therefore, we aimed to investigate the molecular effects of topical metformin application on delayed wound healing, which's common in diabetes. Methods and results: In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-?B p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline. As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-?B p65 activity and diminishing the expression of MMP2 and MMP9. Conclusions: Diabetic wounds treated with metformin healed even faster than those in the control group that mimicked standard wound healing.