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Downregulation of Mir-542-3P Contributes to Apoptosis Resistance in Dermal Fibroblasts From Systemic Sclerosis Patients Via Survivin Overexpression Pubmed



Manesh PV1, 3 ; Farazmand A1 ; Gharibdoost F3 ; Vanaki N3 ; Mostafaei S2 ; Kavosi H3 ; Mahmoudi MB3 ; Mahmoudi M3
Authors
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Authors Affiliations
  1. 1. Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran
  2. 2. Department of Community Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
  3. 3. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, 1411713137, Iran

Source: Iranian Journal of Allergy# Asthma and Immunology Published:2019


Abstract

Systemic sclerosis (SSc) is characterized by excessive production of collagens by fibroblasts that leads to vast fibrosis. Resistance to apoptosis is one of the possible underlying mechanisms of fibrosis in these patients. Survivinis involved in inhibition of apoptosis and aberrantly functions in SSc. Since dysregulation of survivin-targeting microRNAs (miRNAs) has frequently been observed in cancer and some autoimmune disorders, this study aimed to investigate their expression status in dermal fibroblasts from SSc patients. DiffuseSSc patients were selected according to American College of Rheumatology criteria. Isolated fibroblasts from 10 SSc and 10 healthy skin biopsies were cultured. After examining purity of the cells, mRNA and miRNAs extraction was performed followed by complementary DNA (cDNA) synthesis. Relative expressions ofsurvivin mRNA, miR-16-5p, miR-320a, miR-218-5p, miR-708-5p and miR-542-3p were analyzed using real time PCR. Survivin mRNA expression was significantly 1.85-fold upregulated in fibroblasts from SSc patients compared with healthy controls (p=0.046). Among the studied miRNAs, miR-542-3p expression was significantly decreased (p=0.033), while enhanced expression of miR-708-5p was observed in SSc fibroblasts (p=0.05) in comparison to healthy subjects. Downregulation of miR-542-3p significantly correlated with survivin overexpression (r=0.45, p=0.049). Downregulation of miR-542-3p that is correlated with higher surviving expression levels might be a possible cause of apoptosis resistance in SSc fibroblasts, hence providing a new understanding of the disease pathogenesis. Copyright© April 2019, Iran J Allergy Asthma Immunol. All rights reserved.
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