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AB0168 Protective effects of epigallocatechin 3 gallate on fibrosis in scleroderma model
  1. A Kocak1,
  2. D Harmancı1,
  3. M Birlik2,
  4. S Sarioglu3,
  5. G Guner Akdogan4
  1. 1Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University
  2. 2Department of Internal Medicine, Division of Rheumatology & Immunology
  3. 3Department of Medical Pathology, School of Medicine, Dokuz Eylul University
  4. 4Department of Biochemistry, School of Medicine, Izmir University of Economics, Izmir, Turkey

Abstract

Background Scleroderma (SSc) is a disease that shows involvement in internal organs or on the skin characterized by fibrosis (1). Dermis thickening and uncontrolled extracellular matrix (ECM) increase are seen in this disease whose pathogenesis is not fully understood. TGF-β/Smad 2&3 pathway is pivotal role in SSc pathogenesis via induction of profibrotic molecules including collagen and by decrease of matrix metalloproteinases (MMPs) synthesis (2,3). The occurrence of the myofibroblast phenotype at fibrosis is thought to be responsible for the contracted regions of the affected tissues (4).

Objectives The aim of this study with bleomycin (BLM) formed in an experimental model of scleroderma is to investigate the potential effects of epigallocatechin-3-gallate (EGCG) against fibrosis.

Methods 32 Balb/c female mice were randomly selected into four groups.For 21 days: (1) Control group (n: 8) was given 100 μ L subcutan (sc) saline (SF) once a day, 100 μL intraperitoneal (ip) SF twice a week, (2) BLM group (n: 8) was given 100 μL (100 ug) sc BLM once a day, 100 μL ip SF twice a week, (3) BLM + EGCG group (n:8) was given 100 μL (100 ug) sc BLM once a day, 100 μL (100 μg) ip EGCG twice a week, (4) EGCG group (n: 8) was given 100 μL sc SF once a day, 100 mL (100 μg) ip ECCG twice a week. Hematoxylin&eosin and Masson trichrome staining of dermal areas were performed. Myofibroblast activity was measured using alpha smooth muscle actin antibody (αSMA) by immunohistochemistry.Expression levels of MMP-1, MMP-8, MMP-13 and p-SMAD protein were examined by western blot. Expression levels of TGF-β mRNA were examined by qPCR. All of the statistical analyses were performed using SPSS software and the quantitative data were expressed as the means±SEM.The quantitative variables were compared using the a ANOVA-Sidak. Statistical significance was defined as p<0.05

Results When compared to sham,control and experimental groups was observed to have reduced connective tissue fibrosis in dermis area, according to Masson Trichrome results. EGCG group showed a significant reduction in fibrosis at the dermal surface area with respect to hematoxylin measurements. MMP-1, MMP-8, p-SMAD 2/3 protein levels and TGF- β mRNA expression were slightly decreased in EGCG Group compared with the other tested groups (p<0.05). Otherwise, MMP-13 wasn't change between groups.

Conclusions This study contributes to the potential use of EGCG as a treatment for fibrosis in SSc patients. Also, MMP-1&MMP-8 may play an important role in the etiology of SSc.

References

  1. Varga, J. 2012. 15. Scleroderma-from pathogenesis to comprehensive management.Varga, J., Denton, C., Wigley, F.M./Denton C. New York: Springer.

  2. Ihn H. 2008. Autocrine TGF-beta signaling in the pathogenesis of systemic sclerosis. J Dermatol Sci 49: 103–113.

  3. Derk CT. 2007. Transforming growth factor-beta (TGF-beta) and its role in the pathogenesis of systemic sclerosis: a novel target for therapy? Recent Pat Inflamm Allergy Drug Discov 1: 142–145.

  4. Desmouliere A, Chaponnier C, Gabbiani G. 2005. Tissue repair, contraction, and the myofibroblast. Wound Repair Regen. 13(1):7–12.

References

Acknowledgements This research was supported by a grant supplied from “Dokuz Eylul University Research Fund” and carried out at Dokuz Eylul University Medicine Faculty of Research Laboratory (R-LAB).

Disclosure of Interest None declared

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