Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis

被引：69

作者：

Chouri, Eleni ^{[1
,2
]}

Servaas, Nila H. ^{[1
,2
]}

Bekker, Cornelis P. J. ^{[1
,2
]}

Affandi, Alsya J. ^{[1
,2
]}

Cossu, Marta ^{[1
,2
]}

Hillen, Maarten R. ^{[1
,2
]}

Angiolilli, Chiara ^{[1
,2
]}

Mertens, Jorre S. ^{[1
,2
]}

van den Hoogen, Lucas L. ^{[1
,2
]}

Silva-Cardoso, Sandra ^{[1
,2
]}

van der Kroef, Maarten ^{[1
,2
]}

Vazirpanah, Nadia ^{[1
,2
]}

Wichers, Catharina G. K. ^{[1
,2
]}

Carvalheiro, Tiago ^{[1
,2
]}

Blokland, Sofie L. M. ^{[1
,2
]}

Giovannone, Barbara ^{[2
,3
]}

Porretti, Laura ^{[4
]}

Marut, Wioleta ^{[1
,2
]}

Vigone, Barbara ^{[5
]}

van Roon, Joel A. G. ^{[1
,2
]}

Beretta, Lorenzo ^{[5
]}

Rossato, Marzia ^{[1
,2
,6
]}

Radstake, Timothy R. D. J. ^{[1
,2
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, Utrecht, Netherlands

[2] Univ Utrecht, Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Dept Dermatol Allergol, Utrecht, Netherlands

[4] Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Clin Chem & Microbiol Lab, Flow Cytometry Serv, Milan, Italy

[5] Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Referral Ctr Syst Autoimmune Dis, Scleroderma Unit, Milan, Italy

[6] Univ Verona, Dept Biotechnol, Verona, Italy

来源：

JOURNAL OF AUTOIMMUNITY | 2018年 / 89卷

基金：

欧洲研究理事会;

关键词：

Systemic sclerosis; Circulating microRNAs; miR-483-5p; Fibrosis; INTERSTITIAL LUNG-DISEASE; DOWN-REGULATION; DERMAL FIBROBLASTS; I COLLAGEN; SCLERODERMA; EXPRESSION; CLASSIFICATION; PATHOGENESIS; CONTRIBUTES; CELLS;

D O I：

10.1016/j.jaut.2017.12.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential bio-markers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. Methods: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells. Results: 30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes. Conclusions: Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc. (C) 2018 The Authors. Published by Elsevier Ltd.

引用

页码：162 / 170

页数：9

共 35 条

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