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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

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Abstract

Aims

Lucilia 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.

Methods

The 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.

Results

The 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).

Conclusion

ES 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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Acknowledgements

The concept and design of research belong to FKT and GSK. Animal experiments were carried out by FKT and MT, ES preparation by FKT, EP, and SS, RT-PCR was conducted by FKT and EC. TS and EYS carried out the immunohistochemical analysis. FKT, TS, and EYS performed data analysis, interpretation and writing the article, supervised by GSK. This work was supported by the Scientific Research Project Coordination Unit of Istanbul University (Project number: 35048).

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Authors and Affiliations

  1. Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Fatma Kübra Tombulturk, Tugba Soydas & Matem Tuncdemir

  2. Medical Laboratory Techniques, Vocational School of Health Services, Istinye University, Istanbul, Turkey

    Fatma Kübra Tombulturk

  3. Department of Histology and Embryology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

    Elif Yaprak Sarac

  4. Department of Medical Biology, Medical Faculty, Saglik Bilimleri University, Istanbul, Turkey

    Ender Coskunpinar

  5. Department of Medical Microbiology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Erdal Polat

  6. Department of Biotherapy Research and Development Laboratory, Istanbul University, Istanbul, Turkey

    Serhat Sirekbasan

  7. Department of Medical Biology and Genetics, Istanbul Aydin University, Medical Faculty, Sefakoy-Kucukcekmece, 34295, Istanbul, Turkey

    Tugba Soydas & Gonul Kanigur-Sultuybek

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  1. Fatma Kübra Tombulturk
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  2. Tugba Soydas
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Correspondence to Gonul Kanigur-Sultuybek.

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All authors stated that there is no conflict of interests that could be perceived as prejudicing the impartiality of the research reported.

Ethical standard statement

All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Ethical Committee of Istanbul University (Approval no. 2013/39).

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Tombulturk, F.K., Soydas, T., Sarac, E.Y. et al. 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. Acta Diabetol 56, 177–186 (2019). https://doi.org/10.1007/s00592-018-1237-5

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  • DOI: https://doi.org/10.1007/s00592-018-1237-5

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