Functional role of an islet transcription factor, INSM1/IA-1, on pancreatic acinar cell trans-differentiation.
J Cell Physiol
; 227(6): 2470-9, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-21830214
ABSTRACT
In this study, the functional role of INSM1 is examined with an AR42J acinar cell model for trans-differentiation into insulin-positive cells. Islet transcription factors (ITFs INSM1, Pdx-1, and NeuroD1) are over-expressed in AR42J cells using adenoviral vectors. Addition of Ad-INSM1 alone or the combination of three ITFs to the AR42J cells triggers cellular trans-differentiation. Ectopic expression of INSM1 directly induces insulin, Pax6, and Nkx6.1 expression, whereas Pdx-1 and NeuroD1 were slightly suppressed by INSM1. Addition of Pdx-1 and NeuroD1 with INSM1 further enhances endocrine trans-differentiation by increasing both the numbers and intensity of the insulin-positive cells with simultaneous activation of ITFs, Ngn3 and MafA. INSM1 expression alone partially inhibits dexamethasone-induced exocrine amylase expression. The combination of the three ITFs completely inhibits amylase expression and concomitantly induces greater acinar cell trans-differentiation into endocrine cells. Also, addition of the three ITFs promotes EGF and TGFß receptors expression. Stimulation by the three ITFs along with the EGF/TGFß growth factors strongly promotes insulin gene expression. The combination of the three ITFs and EGF/TGFß growth factors with the primary cultured pancreatic acini also facilitates exocrine to endocrine cell differentiation. Taken together, both the AR42J cell line and the primary cultured mouse acinar cells support INSM1 induced acini trans-differentiation model.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Ilhotas Pancreáticas
/
Transdiferenciação Celular
/
Células Acinares
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos