Coxsackievirus B Type 4 Infection in β Cells Downregulates the Chaperone Prefoldin URI to Induce a MODY4-like Diabetes via
Animals
Capsid Proteins
/ genetics
Coxsackievirus Infections
/ genetics
DNA (Cytosine-5-)-Methyltransferase 1
/ antagonists & inhibitors
Diabetes Mellitus, Type 2
/ genetics
Disease Models, Animal
Enterovirus B, Human
/ genetics
Female
Gene Expression Regulation
Glucose
/ metabolism
Homeodomain Proteins
/ genetics
Humans
Insulin-Secreting Cells
/ drug effects
Male
Mice
Mice, Transgenic
Procainamide
/ pharmacology
Rats
Repressor Proteins
/ genetics
Signal Transduction
Trans-Activators
/ genetics
Transplantation, Heterologous
DNMT1
PDX1
beta cells
coxsackievirus B Type 4
diabetes
enteroviruses
estrogen receptor
hypermethylation
prefoldin URI
transdifferentiation
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
20 10 2020
20 10 2020
Historique:
received:
29
06
2018
revised:
06
08
2020
accepted:
22
09
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
19
11
2020
Statut:
epublish
Résumé
Enteroviruses are suspected to contribute to insulin-producing β cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice and in rat insulinoma cells displays loss of unconventional prefoldin RPB5 interactor (URI) and PDX1, affecting β cell function and identity. Genetic URI ablation in the mouse pancreas causes PDX1 depletion in β cells. Importantly, diabetic PDX1 heterozygous mice overexpressing URI in β cells are more glucose tolerant. Mechanistically, URI loss triggers estrogen receptor nuclear translocation leading to DNA methyltransferase 1 (DNMT1) expression, which induces
Identifiants
pubmed: 33205075
doi: 10.1016/j.xcrm.2020.100125
pii: S2666-3791(20)30167-1
pmc: PMC7659558
doi:
Substances chimiques
Capsid Proteins
0
Homeodomain Proteins
0
Repressor Proteins
0
Trans-Activators
0
Uri1 protein, mouse
0
VP1 protein, enterovirus B
0
pancreatic and duodenal homeobox 1 protein
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
Dnmt1 protein, mouse
EC 2.1.1.37
Glucose
IY9XDZ35W2
Procainamide
L39WTC366D
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
100125Subventions
Organisme : NIAID NIH HHS
ID : R01 AI116920
Pays : United States
Informations de copyright
© 2020 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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