טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSafieh Mirna
SubjectRole of EMMPRIN/CD147 in the Pathogenesis of Psoriatic
Arthritis
DepartmentDepartment of Medicine
Supervisors Dr. Michal Rahat
Dr. Devy Zisman
Full Thesis textFull thesis text - English Version


Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis. Angiogenesis in the joint is an essential component of disease progression, enabling synovium growth and recruitment of leukocytes into the site of inflammation.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a multifunctional protein that can enhance angiogenesis by inducing VEGF and different MMPs. Increased EMMPRIN levels were reported in rheumatoid arthritis (RA) patients, but its involvement in PsA is still unknown.

Our aims were to measure the concentrations of selected angiogenic factors in serum samples obtained from PsA patients and compare them to RA patients and healthy volunteers. In addition, we want to demonstrate the involvement of EMMPRIN and both miRNA-146a and miRNA-203 in the regulation of macrophage-synoviocyte interactions and angiogenesis in vitro.

Blood samples were collected from 97 PsA patients, 33 RA patients and 33 healthy individuals, and the serum was evaluated using ELISA kits for the concentrations of selected angiogenic (EMMPRIN, VEGF, MMP-9, MMP-7, MMP-3, MMP-2, MMP-14, TIMP1  and TIMP-2) and inflammatory factors (TNFα, TGFβ, IL-17, IL-6 and nitric oxide). An in vitro co-culture system that consists of fibroblasts (HT1080) and monocytes (either MM6 or U937), cell lines, with or without TNFα (1ng/ml), was compared to each single cell culture alone. The expression of miRNA-146a and miRNA-203 in the co-cultured was quantified using real-time PCR, and their regulatory effects on EMMPRIN and other angiogenic factors were assessed by transfecting the fibroblast cells with miRNA mimics.