A preliminary study of possible fibrotic role of meprin metalloproteases in scleroderma patients

Ayşe Koçak1, Aydan Köken Avşar2, Duygu Harmancı1, Gül Akdoğan3, A. Merih Birlik2

1Department of Molecular Medicine, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
2Department of Internal Medicine, Division of Rheumatology & Immunology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
3Department of Medical Biochemistry, Izmir University of Economics, Izmir, Turkey

Keywords: Activator protein-1, meprin-alpha, meprin-beta, scleroderma

Abstract

Objectives: This study aims to investigate the possible fibrotic role of meprin metalloproteases and possible fibrotic effects of activator protein-1 (AP-1) in scleroderma patients.

Patients and methods: Between April 2018 and April 2019, a total of 85 scleroderma patients (9 males, 76 females; mean age: 54.9 years; range, 22 to 80 years) who met the 2013 American College of Rheumatology/European League Against Rheumatism criteria and 80 healthy control individuals (10 males, 70 females; mean age 42.9 years; range, 19 to 65 years) were included. Patients’ data and blood samples were collected. Messenger ribonucleic acid expressions of interleukin (IL)-6, AP-1 subunits, and tumor necrosis factor-alpha (TNF-α) were analyzed by quantitative real-time polymerase chain reaction. Serum meprin alpha and beta protein levels were analyzed using the enzyme-linked immunosorbent assay.

Results: Meprin alpha and meprin beta protein levels increased in scleroderma patients. The AP-1 subunits (c-Fos, c-Jun), IL-6, and TNF-α increased in scleroderma patients, compared to controls.

Conclusion: Our results provide evidence showing that increased meprins levels may be related to AP-1 levels and increased meprins levels may responsible for increased inflammatory TNF-α and IL-6 levels. All these data suggest meprins as promising therapeutic targets to restore the balance between inflammation and extracellular matrix deposition in scleroderma.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This study was funded by Dokuz Eylül University Scientific Research Commission (2018.KB.SAG.050).