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The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes

Belgardt, Bengt-Frederik
Ahmed, Kashan
Spranger, Martina
Latreille, Mathieu
Denzler, Remy
Kondratiuk, Nadiia
von Meyenn, Ferdinand
Villena, Felipe Nunez
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Published in Nature Medicine. 2015, vol. 21, no. 6, p. 619-627
Abstract Pancreatic beta cell death is a hallmark of type 1 (T1D) and type 2 (T2D) diabetes, but the molecular mechanisms underlying this aspect of diabetic pathology are poorly understood. Here we report that expression of the microRNA (miR)-200 family is strongly induced in islets of diabetic mice and that beta cell-specific overexpression of miR-200 in mice is sufficient to induce beta cell apoptosis and lethal T2D. Conversely, mir-200 ablation in mice reduces beta cell apoptosis and ameliorates T2D. We show that miR-200 negatively regulates a conserved anti-apoptotic and stress-resistance network that includes the essential beta cell chaperone Dnajc3 (also known as p58IPK) and the caspase inhibitor Xiap. We also observed that mir-200 dosage positively controls activation of the tumor suppressor Trp53 and thereby creates a pro-apoptotic gene-expression signature found in islets of diabetic mice. Consequently, miR-200-induced T2D is suppressed by interfering with the signaling of Trp53 and Bax, a proapoptotic member of the B cell lymphoma 2 protein family. Our results reveal a crucial role for the miR-200 family in beta cell survival and the pathophysiology of diabetes.
PMID: 25985365
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Research groups Transplantation et hépatologie (905)
Chirurgie viscérale (104)
Chirurgie viscérale (HUG)
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BELGARDT, Bengt-Frederik et al. The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. In: Nature Medicine, 2015, vol. 21, n° 6, p. 619-627. doi: 10.1038/nm.3862 https://archive-ouverte.unige.ch/unige:90599

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Deposited on : 2016-12-21

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