STAT3 suppression and ß-cell ablation enhance α-to-ß reprogramming mediated by Pdx1.
Sci Rep
; 12(1): 21419, 2022 Dec 10.
Article
en En
| MEDLINE
| ID: mdl-36496541
ABSTRACT
As diabetes results from the absolute or relative deficiency of insulin secretion from pancreatic ß cells, possible methods to efficiently generate surrogate ß cells have attracted a lot of efforts. To date, insulin-producing cells have been generated from various differentiated cell types in the pancreas, such as acinar cells and α cells, by inducing defined transcription factors, such as PDX1 and MAFA, yet it is still challenging as to how surrogate ß cells can be efficiently generated for establishing future regenerative therapies for diabetes. In this study, we demonstrated that the exogenous expression of PDX1 activated STAT3 in α cells in vitro, and STAT3-null PDX1-expressing α cells in vivo resulted in efficient induction of α-to-ß reprogramming, accompanied by the emergence of α-cell-derived insulin-producing cells with silenced glucagon expression. Whereas ß-cell ablation by alloxan administration significantly increased the number of α-cell-derived insulin-producing cells by PDX1, STAT3 suppression resulted in no further increase in ß-cell neogenesis after ß-cell ablation. Thus, STAT3 modulation and ß-cell ablation nonadditively enhance α-to-ß reprogramming induced by PDX1, which may lead to the establishment of cell therapies for curing diabetes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus
/
Células Secretoras de Glucagón
/
Células Secretoras de Insulina
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón