Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding

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Standard

Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding. / Urizar, Adriana Ibarra; Prause, Michala; Ingerslev, Lars Roed; Wortham, Matthew; Sui, Yinghui; Sander, Maike; Williams, Kristine; Barrès, Romain; Larsen, Martin R.; Christensen, Gitte Lund; Billestrup, Nils.

I: Cell Death and Disease, Bind 14, Nr. 7, 399, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Urizar, AI, Prause, M, Ingerslev, LR, Wortham, M, Sui, Y, Sander, M, Williams, K, Barrès, R, Larsen, MR, Christensen, GL & Billestrup, N 2023, 'Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding', Cell Death and Disease, bind 14, nr. 7, 399. https://doi.org/10.1038/s41419-023-05906-w

APA

Urizar, A. I., Prause, M., Ingerslev, L. R., Wortham, M., Sui, Y., Sander, M., Williams, K., Barrès, R., Larsen, M. R., Christensen, G. L., & Billestrup, N. (2023). Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding. Cell Death and Disease, 14(7), [399]. https://doi.org/10.1038/s41419-023-05906-w

Vancouver

Urizar AI, Prause M, Ingerslev LR, Wortham M, Sui Y, Sander M o.a. Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding. Cell Death and Disease. 2023;14(7). 399. https://doi.org/10.1038/s41419-023-05906-w

Author

Urizar, Adriana Ibarra ; Prause, Michala ; Ingerslev, Lars Roed ; Wortham, Matthew ; Sui, Yinghui ; Sander, Maike ; Williams, Kristine ; Barrès, Romain ; Larsen, Martin R. ; Christensen, Gitte Lund ; Billestrup, Nils. / Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding. I: Cell Death and Disease. 2023 ; Bind 14, Nr. 7.

Bibtex

@article{c7c63876d8bd46048f187dc82a8addb6,
title = "Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding",
abstract = "Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from individuals with diabetes and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1, and Hey-1 which are transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism by which BMP-2 induces beta cell dysfunction and loss of cell maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired glucose-stimulated insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of cell maturity and proliferation markers specific to the beta cell such as Ins1, Ucn3, and Ki67 and increased expression of Id1-4, Hes-1, and Hey-1. The top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2-induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2 induces loss of beta cell maturity and suggest that remodeling of H3K27ac and decreased NeuroD1 DNA binding activity participate in the effect of BMP-2 on beta cell dysfunction.",
author = "Urizar, {Adriana Ibarra} and Michala Prause and Ingerslev, {Lars Roed} and Matthew Wortham and Yinghui Sui and Maike Sander and Kristine Williams and Romain Barr{\`e}s and Larsen, {Martin R.} and Christensen, {Gitte Lund} and Nils Billestrup",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s41419-023-05906-w",
language = "English",
volume = "14",
journal = "Cell Death & Disease",
issn = "2041-4889",
publisher = "nature publishing group",
number = "7",

}

RIS

TY - JOUR

T1 - Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding

AU - Urizar, Adriana Ibarra

AU - Prause, Michala

AU - Ingerslev, Lars Roed

AU - Wortham, Matthew

AU - Sui, Yinghui

AU - Sander, Maike

AU - Williams, Kristine

AU - Barrès, Romain

AU - Larsen, Martin R.

AU - Christensen, Gitte Lund

AU - Billestrup, Nils

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from individuals with diabetes and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1, and Hey-1 which are transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism by which BMP-2 induces beta cell dysfunction and loss of cell maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired glucose-stimulated insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of cell maturity and proliferation markers specific to the beta cell such as Ins1, Ucn3, and Ki67 and increased expression of Id1-4, Hes-1, and Hey-1. The top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2-induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2 induces loss of beta cell maturity and suggest that remodeling of H3K27ac and decreased NeuroD1 DNA binding activity participate in the effect of BMP-2 on beta cell dysfunction.

AB - Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from individuals with diabetes and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1, and Hey-1 which are transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism by which BMP-2 induces beta cell dysfunction and loss of cell maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired glucose-stimulated insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of cell maturity and proliferation markers specific to the beta cell such as Ins1, Ucn3, and Ki67 and increased expression of Id1-4, Hes-1, and Hey-1. The top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2-induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2 induces loss of beta cell maturity and suggest that remodeling of H3K27ac and decreased NeuroD1 DNA binding activity participate in the effect of BMP-2 on beta cell dysfunction.

U2 - 10.1038/s41419-023-05906-w

DO - 10.1038/s41419-023-05906-w

M3 - Journal article

C2 - 37407581

AN - SCOPUS:85163983993

VL - 14

JO - Cell Death & Disease

JF - Cell Death & Disease

SN - 2041-4889

IS - 7

M1 - 399

ER -

ID: 360607372