Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding - Archive ouverte HAL
Article Dans Une Revue Cell Death and Disease Année : 2023

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

Adriana Ibarra Urizar
Michala Prause
  • Fonction : Auteur
Lars Roed Ingerslev
Matthew Wortham
  • Fonction : Auteur
Yinghui Sui
  • Fonction : Auteur
Kristine Williams
  • Fonction : Auteur
Gitte Lund Christensen
  • Fonction : Auteur
Nils Billestrup

Résumé

Summary 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.

Dates et versions

hal-04311624 , version 1 (28-11-2023)

Identifiants

Citer

Adriana Ibarra Urizar, Michala Prause, Lars Roed Ingerslev, Matthew Wortham, Yinghui Sui, et al.. 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), pp.399. ⟨10.1038/s41419-023-05906-w⟩. ⟨hal-04311624⟩
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