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

Eleni Chouri, Nila H. Servaas, Cornelis P.J. Bekker, Alsya J. Affandi, Marta Cossu, Maarten R. Hillen, Chiara Angiolilli, Jorre S. Mertens, Lucas L. van den Hoogen, Sandra Silva-Cardoso, Maarten van der Kroef, Nadia Vazirpanah, Catharina G.K. Wichers, Tiago Carvalheiro, Sofie L.M. Blokland, Barbara Giovannone, Laura Porretti, Wioleta Marut, Barbara Vigone, Joel A.G. van RoonLorenzo Beretta, Marzia Rossato, Timothy R.D.J. Radstake

Research output: Contribution to journalArticle

Abstract

Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers 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 Sjögren'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.

Original languageEnglish
Pages (from-to)162-170
JournalJournal of Autoimmunity
Volume89
DOIs
Publication statusPublished - 2018

Fingerprint

Systemic Scleroderma
MicroRNAs
Fibrosis
Serum
Localized Scleroderma
Systemic Lupus Erythematosus
Endothelial Cells
Fibroblasts
Skin
Rheumatic Diseases
Biomarkers
Tissue Donors
Lung

Keywords

  • Circulating microRNAs
  • Fibrosis
  • MiR-483-5p
  • Systemic sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chouri, E., Servaas, N. H., Bekker, C. P. J., Affandi, A. J., Cossu, M., Hillen, M. R., ... Radstake, T. R. D. J. (2018). Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis. Journal of Autoimmunity, 89, 162-170. https://doi.org/10.1016/j.jaut.2017.12.015

Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis. / Chouri, Eleni; Servaas, Nila H.; Bekker, Cornelis P.J.; Affandi, Alsya J.; Cossu, Marta; Hillen, Maarten R.; Angiolilli, Chiara; Mertens, Jorre S.; van den Hoogen, Lucas L.; Silva-Cardoso, Sandra; van der Kroef, Maarten; Vazirpanah, Nadia; Wichers, Catharina G.K.; Carvalheiro, Tiago; Blokland, Sofie L.M.; Giovannone, Barbara; Porretti, Laura; Marut, Wioleta; Vigone, Barbara; van Roon, Joel A.G.; Beretta, Lorenzo; Rossato, Marzia; Radstake, Timothy R.D.J.

In: Journal of Autoimmunity, Vol. 89, 2018, p. 162-170.

Research output: Contribution to journalArticle

Chouri, E, Servaas, NH, Bekker, CPJ, Affandi, AJ, Cossu, M, Hillen, MR, Angiolilli, C, Mertens, JS, van den Hoogen, LL, Silva-Cardoso, S, van der Kroef, M, Vazirpanah, N, Wichers, CGK, Carvalheiro, T, Blokland, SLM, Giovannone, B, Porretti, L, Marut, W, Vigone, B, van Roon, JAG, Beretta, L, Rossato, M & Radstake, TRDJ 2018, 'Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis', Journal of Autoimmunity, vol. 89, pp. 162-170. https://doi.org/10.1016/j.jaut.2017.12.015
Chouri, Eleni ; Servaas, Nila H. ; Bekker, Cornelis P.J. ; Affandi, Alsya J. ; Cossu, Marta ; Hillen, Maarten R. ; Angiolilli, Chiara ; Mertens, Jorre S. ; van den Hoogen, Lucas L. ; Silva-Cardoso, Sandra ; van der Kroef, Maarten ; Vazirpanah, Nadia ; Wichers, Catharina G.K. ; Carvalheiro, Tiago ; Blokland, Sofie L.M. ; Giovannone, Barbara ; Porretti, Laura ; Marut, Wioleta ; Vigone, Barbara ; van Roon, Joel A.G. ; Beretta, Lorenzo ; Rossato, Marzia ; Radstake, Timothy R.D.J. / Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis. In: Journal of Autoimmunity. 2018 ; Vol. 89. pp. 162-170.
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title = "Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis",
abstract = "Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers 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 Sj{\"o}gren'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.",
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T1 - Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis

AU - Chouri, Eleni

AU - Servaas, Nila H.

AU - Bekker, Cornelis P.J.

AU - Affandi, Alsya J.

AU - Cossu, Marta

AU - Hillen, Maarten R.

AU - Angiolilli, Chiara

AU - Mertens, Jorre S.

AU - van den Hoogen, Lucas L.

AU - Silva-Cardoso, Sandra

AU - van der Kroef, Maarten

AU - Vazirpanah, Nadia

AU - Wichers, Catharina G.K.

AU - Carvalheiro, Tiago

AU - Blokland, Sofie L.M.

AU - Giovannone, Barbara

AU - Porretti, Laura

AU - Marut, Wioleta

AU - Vigone, Barbara

AU - van Roon, Joel A.G.

AU - Beretta, Lorenzo

AU - Rossato, Marzia

AU - Radstake, Timothy R.D.J.

PY - 2018

Y1 - 2018

N2 - Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers 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 Sjögren'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.

AB - Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers 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 Sjögren'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.

KW - Circulating microRNAs

KW - Fibrosis

KW - MiR-483-5p

KW - Systemic sclerosis

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