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miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis

BACKGROUND: One of the main issues in pathogenesis of MS is Th17/Treg imbalance. There are growing interests in nominating miRNAs involved in Th17 cell differentiation, suggesting them as new therapeutic agents that may reduce progression of different autoimmune diseases specially MS. OBJECTIVES: We...

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Autores principales: Naghavian, Reza, Ghaedi, Kamran, Kiani-Esfahani, Abbas, Ganjalikhani-Hakemi, Mazdak, Etemadifar, Masoud, Nasr-Esfahani, Mohammad Hossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418573/
https://www.ncbi.nlm.nih.gov/pubmed/25938517
http://dx.doi.org/10.1371/journal.pone.0124555
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author Naghavian, Reza
Ghaedi, Kamran
Kiani-Esfahani, Abbas
Ganjalikhani-Hakemi, Mazdak
Etemadifar, Masoud
Nasr-Esfahani, Mohammad Hossein
author_facet Naghavian, Reza
Ghaedi, Kamran
Kiani-Esfahani, Abbas
Ganjalikhani-Hakemi, Mazdak
Etemadifar, Masoud
Nasr-Esfahani, Mohammad Hossein
author_sort Naghavian, Reza
collection PubMed
description BACKGROUND: One of the main issues in pathogenesis of MS is Th17/Treg imbalance. There are growing interests in nominating miRNAs involved in Th17 cell differentiation, suggesting them as new therapeutic agents that may reduce progression of different autoimmune diseases specially MS. OBJECTIVES: We assessed transcript levels of miR-141 and miR-200a in MS patients, during relapsing and remitting phases. We also investigated possible role of miR-141, miR-200a in inducing differentiation to Th17 cells. MATERIALS AND METHODS: Forty RR-MS patient samples including relapsing (n=20) and remitting (n=20) phases were chosen. Expression level of miR-141 and miR-200a were measured by RT-q PCR and compared to healthy control group (n=10). In-silico analyses on miR-141 and miR-200a targetome showed involvement of both miRNAs in T helper cell differentiation pathways including TGF-β, mTOR and JAK/STAT. RESULTS: We observed that percentage of RORγt(+) CD4(+) T cells increase in relapsing phase while FOXP3(+) CD4(+) increase in remitting phase of MS patients. Furthermore, both miR-141 and miR-200a show up-regulation in relapsing phase of MS patients compared to remitting and control groups. Interestingly, expression level of target genes of miR-141 and miR-200a, which were assessed through in-silico methods, show down-regulation in relapsing phase of MS patients. CONCLUSIONS: According to our results, miR-141 and miR-200a may be key miRNAs in progression of symptoms of MS through inducing differentiation of Th17 cells and inhibiting differentiation to Treg cells. Our data suggest that these miRNAs may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation.
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spelling pubmed-44185732015-05-12 miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis Naghavian, Reza Ghaedi, Kamran Kiani-Esfahani, Abbas Ganjalikhani-Hakemi, Mazdak Etemadifar, Masoud Nasr-Esfahani, Mohammad Hossein PLoS One Research Article BACKGROUND: One of the main issues in pathogenesis of MS is Th17/Treg imbalance. There are growing interests in nominating miRNAs involved in Th17 cell differentiation, suggesting them as new therapeutic agents that may reduce progression of different autoimmune diseases specially MS. OBJECTIVES: We assessed transcript levels of miR-141 and miR-200a in MS patients, during relapsing and remitting phases. We also investigated possible role of miR-141, miR-200a in inducing differentiation to Th17 cells. MATERIALS AND METHODS: Forty RR-MS patient samples including relapsing (n=20) and remitting (n=20) phases were chosen. Expression level of miR-141 and miR-200a were measured by RT-q PCR and compared to healthy control group (n=10). In-silico analyses on miR-141 and miR-200a targetome showed involvement of both miRNAs in T helper cell differentiation pathways including TGF-β, mTOR and JAK/STAT. RESULTS: We observed that percentage of RORγt(+) CD4(+) T cells increase in relapsing phase while FOXP3(+) CD4(+) increase in remitting phase of MS patients. Furthermore, both miR-141 and miR-200a show up-regulation in relapsing phase of MS patients compared to remitting and control groups. Interestingly, expression level of target genes of miR-141 and miR-200a, which were assessed through in-silico methods, show down-regulation in relapsing phase of MS patients. CONCLUSIONS: According to our results, miR-141 and miR-200a may be key miRNAs in progression of symptoms of MS through inducing differentiation of Th17 cells and inhibiting differentiation to Treg cells. Our data suggest that these miRNAs may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation. Public Library of Science 2015-05-04 /pmc/articles/PMC4418573/ /pubmed/25938517 http://dx.doi.org/10.1371/journal.pone.0124555 Text en © 2015 Naghavian et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Naghavian, Reza
Ghaedi, Kamran
Kiani-Esfahani, Abbas
Ganjalikhani-Hakemi, Mazdak
Etemadifar, Masoud
Nasr-Esfahani, Mohammad Hossein
miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis
title miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis
title_full miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis
title_fullStr miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis
title_full_unstemmed miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis
title_short miR-141 and miR-200a, Revelation of New Possible Players in Modulation of Th17/Treg Differentiation and Pathogenesis of Multiple Sclerosis
title_sort mir-141 and mir-200a, revelation of new possible players in modulation of th17/treg differentiation and pathogenesis of multiple sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418573/
https://www.ncbi.nlm.nih.gov/pubmed/25938517
http://dx.doi.org/10.1371/journal.pone.0124555
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