MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage

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Standard

MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage. / Vestergaard, Anna Lindelov; Bang-Berthelsen, Claus Heiner; Floyel, Tina; Stahl, Jonathan Lucien; Christen, Lisa; Sotudeh, Farzaneh Taheri; Horskjaer, Peter de Hemmer; Frederiksen, Klaus Stensgaard; Kofod, Frida Greek; Bruun, Christine; Berchtold, Lukas Adrian; Storling, Joachim; Regazzi, Romano; Kaur, Simranjeet; Pociot, Flemming; Mandrup-Poulsen, Thomas.

I: PLOS ONE, Bind 13, Nr. 9, e0203713 , 27.09.2018, s. 1-22.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Vestergaard, AL, Bang-Berthelsen, CH, Floyel, T, Stahl, JL, Christen, L, Sotudeh, FT, Horskjaer, PDH, Frederiksen, KS, Kofod, FG, Bruun, C, Berchtold, LA, Storling, J, Regazzi, R, Kaur, S, Pociot, F & Mandrup-Poulsen, T 2018, 'MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage', PLOS ONE, bind 13, nr. 9, e0203713 , s. 1-22. https://doi.org/10.1371/journal.pone.0203713

APA

Vestergaard, A. L., Bang-Berthelsen, C. H., Floyel, T., Stahl, J. L., Christen, L., Sotudeh, F. T., Horskjaer, P. D. H., Frederiksen, K. S., Kofod, F. G., Bruun, C., Berchtold, L. A., Storling, J., Regazzi, R., Kaur, S., Pociot, F., & Mandrup-Poulsen, T. (2018). MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage. PLOS ONE, 13(9), 1-22. [e0203713 ]. https://doi.org/10.1371/journal.pone.0203713

Vancouver

Vestergaard AL, Bang-Berthelsen CH, Floyel T, Stahl JL, Christen L, Sotudeh FT o.a. MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage. PLOS ONE. 2018 sep 27;13(9):1-22. e0203713 . https://doi.org/10.1371/journal.pone.0203713

Author

Vestergaard, Anna Lindelov ; Bang-Berthelsen, Claus Heiner ; Floyel, Tina ; Stahl, Jonathan Lucien ; Christen, Lisa ; Sotudeh, Farzaneh Taheri ; Horskjaer, Peter de Hemmer ; Frederiksen, Klaus Stensgaard ; Kofod, Frida Greek ; Bruun, Christine ; Berchtold, Lukas Adrian ; Storling, Joachim ; Regazzi, Romano ; Kaur, Simranjeet ; Pociot, Flemming ; Mandrup-Poulsen, Thomas. / MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage. I: PLOS ONE. 2018 ; Bind 13, Nr. 9. s. 1-22.

Bibtex

@article{6fb8ab7ddbee4ea0b5986c25260ee204,
title = "MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage",
abstract = "Inflammatory β-cell failure contributes to type 1 and type 2 diabetes pathogenesis. Pro-inflammatory cytokines cause β-cell dysfunction and apoptosis, and lysine deacetylase inhibitors (KDACi) prevent β-cell failure in vitro and in vivo, in part by reducing NF-κB transcriptional activity. We investigated the hypothesis that the protective effect of KDACi involves transcriptional regulation of microRNAs (miRs), potential new targets in diabetes treatment. Insulin-producing INS1 cells were cultured with or without the broad-spectrum KDACi Givinostat, prior to exposure to the pro-inflammatory cytokines IL-1β and IFN-γ for 6 h or 24 h, and miR expression was profiled with miR array. Thirteen miRs (miR-7a-2-3p, miR-29c-3p, miR-96-5p, miR-101a-3p, miR-140-5p, miR-146a-5p, miR-146b-5p, miR-340-5p, miR-384-5p, miR-455-5p, miR-466b-2-3p, miR-652-5p, and miR-3584-5p) were regulated by both cytokines and Givinostat, and nine were examined by qRT-PCR. miR-146a-5p was strongly regulated by cytokines and KDACi and was analyzed further. miR-146a-5p expression was induced by cytokines in rat and human islets. Cytokine-induced miR-146a-5p expression was specific for INS1 and β-TC3 cells, whereas α-TC1 cells exhibited a higher basal expression. Transfection of INS1 cells with miR-146a-5p reduced cytokine signaling, including the activity of NF-κB and iNOS promoters, as well as NO production and protein levels of iNOS and its own direct targets TNF receptor associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1). miR-146a-5p was elevated in the pancreas of diabetes-prone BB-DP rats at diabetes onset, suggesting that miR-146a-5p could play a role in type 1 diabetes development. The miR array of cytokine-exposed INS1 cells rescued by KDACi revealed several other miRs potentially involved in cytokine-induced β-cell apoptosis, demonstrating the strength of this approach.",
author = "Vestergaard, {Anna Lindelov} and Bang-Berthelsen, {Claus Heiner} and Tina Floyel and Stahl, {Jonathan Lucien} and Lisa Christen and Sotudeh, {Farzaneh Taheri} and Horskjaer, {Peter de Hemmer} and Frederiksen, {Klaus Stensgaard} and Kofod, {Frida Greek} and Christine Bruun and Berchtold, {Lukas Adrian} and Joachim Storling and Romano Regazzi and Simranjeet Kaur and Flemming Pociot and Thomas Mandrup-Poulsen",
year = "2018",
month = sep,
day = "27",
doi = "10.1371/journal.pone.0203713",
language = "English",
volume = "13",
pages = "1--22",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage

AU - Vestergaard, Anna Lindelov

AU - Bang-Berthelsen, Claus Heiner

AU - Floyel, Tina

AU - Stahl, Jonathan Lucien

AU - Christen, Lisa

AU - Sotudeh, Farzaneh Taheri

AU - Horskjaer, Peter de Hemmer

AU - Frederiksen, Klaus Stensgaard

AU - Kofod, Frida Greek

AU - Bruun, Christine

AU - Berchtold, Lukas Adrian

AU - Storling, Joachim

AU - Regazzi, Romano

AU - Kaur, Simranjeet

AU - Pociot, Flemming

AU - Mandrup-Poulsen, Thomas

PY - 2018/9/27

Y1 - 2018/9/27

N2 - Inflammatory β-cell failure contributes to type 1 and type 2 diabetes pathogenesis. Pro-inflammatory cytokines cause β-cell dysfunction and apoptosis, and lysine deacetylase inhibitors (KDACi) prevent β-cell failure in vitro and in vivo, in part by reducing NF-κB transcriptional activity. We investigated the hypothesis that the protective effect of KDACi involves transcriptional regulation of microRNAs (miRs), potential new targets in diabetes treatment. Insulin-producing INS1 cells were cultured with or without the broad-spectrum KDACi Givinostat, prior to exposure to the pro-inflammatory cytokines IL-1β and IFN-γ for 6 h or 24 h, and miR expression was profiled with miR array. Thirteen miRs (miR-7a-2-3p, miR-29c-3p, miR-96-5p, miR-101a-3p, miR-140-5p, miR-146a-5p, miR-146b-5p, miR-340-5p, miR-384-5p, miR-455-5p, miR-466b-2-3p, miR-652-5p, and miR-3584-5p) were regulated by both cytokines and Givinostat, and nine were examined by qRT-PCR. miR-146a-5p was strongly regulated by cytokines and KDACi and was analyzed further. miR-146a-5p expression was induced by cytokines in rat and human islets. Cytokine-induced miR-146a-5p expression was specific for INS1 and β-TC3 cells, whereas α-TC1 cells exhibited a higher basal expression. Transfection of INS1 cells with miR-146a-5p reduced cytokine signaling, including the activity of NF-κB and iNOS promoters, as well as NO production and protein levels of iNOS and its own direct targets TNF receptor associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1). miR-146a-5p was elevated in the pancreas of diabetes-prone BB-DP rats at diabetes onset, suggesting that miR-146a-5p could play a role in type 1 diabetes development. The miR array of cytokine-exposed INS1 cells rescued by KDACi revealed several other miRs potentially involved in cytokine-induced β-cell apoptosis, demonstrating the strength of this approach.

AB - Inflammatory β-cell failure contributes to type 1 and type 2 diabetes pathogenesis. Pro-inflammatory cytokines cause β-cell dysfunction and apoptosis, and lysine deacetylase inhibitors (KDACi) prevent β-cell failure in vitro and in vivo, in part by reducing NF-κB transcriptional activity. We investigated the hypothesis that the protective effect of KDACi involves transcriptional regulation of microRNAs (miRs), potential new targets in diabetes treatment. Insulin-producing INS1 cells were cultured with or without the broad-spectrum KDACi Givinostat, prior to exposure to the pro-inflammatory cytokines IL-1β and IFN-γ for 6 h or 24 h, and miR expression was profiled with miR array. Thirteen miRs (miR-7a-2-3p, miR-29c-3p, miR-96-5p, miR-101a-3p, miR-140-5p, miR-146a-5p, miR-146b-5p, miR-340-5p, miR-384-5p, miR-455-5p, miR-466b-2-3p, miR-652-5p, and miR-3584-5p) were regulated by both cytokines and Givinostat, and nine were examined by qRT-PCR. miR-146a-5p was strongly regulated by cytokines and KDACi and was analyzed further. miR-146a-5p expression was induced by cytokines in rat and human islets. Cytokine-induced miR-146a-5p expression was specific for INS1 and β-TC3 cells, whereas α-TC1 cells exhibited a higher basal expression. Transfection of INS1 cells with miR-146a-5p reduced cytokine signaling, including the activity of NF-κB and iNOS promoters, as well as NO production and protein levels of iNOS and its own direct targets TNF receptor associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1). miR-146a-5p was elevated in the pancreas of diabetes-prone BB-DP rats at diabetes onset, suggesting that miR-146a-5p could play a role in type 1 diabetes development. The miR array of cytokine-exposed INS1 cells rescued by KDACi revealed several other miRs potentially involved in cytokine-induced β-cell apoptosis, demonstrating the strength of this approach.

U2 - 10.1371/journal.pone.0203713

DO - 10.1371/journal.pone.0203713

M3 - Journal article

C2 - 30260972

VL - 13

SP - 1

EP - 22

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 9

M1 - e0203713

ER -

ID: 210015663