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


Tombulturk F. K. , Soydas T., Sarac E. Y. , TUNÇDEMİR M., Coskunpinar E., POLAT E., ...More

ACTA DIABETOLOGICA, vol.56, no.2, pp.177-186, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 56 Issue: 2
  • Publication Date: 2019
  • Doi Number: 10.1007/s00592-018-1237-5
  • Title of Journal : ACTA DIABETOLOGICA
  • Page Numbers: pp.177-186

Abstract

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.