Document Detail


Functional role of an islet transcription factor, INSM1/IA-1, on pancreatic acinar cell trans-differentiation.
MedLine Citation:
PMID:  21830214     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 TGFβ receptors expression. Stimulation by the three ITFs along with the EGF/TGFβ growth factors strongly promotes insulin gene expression. The combination of the three ITFs and EGF/TGFβ 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.
Authors:
Tao Zhang; Nicolle A Saunee; Mary B Breslin; Kejing Song; Michael S Lan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  227     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-02-27     Completed Date:  2012-04-19     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2470-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Affiliation:
The Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA.
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MeSH Terms
Descriptor/Qualifier:
Acinar Cells / drug effects,  metabolism*,  pathology
Adenoviridae / genetics
Amylases / metabolism
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Cell Line, Tumor
Cell Transdifferentiation* / drug effects
Cricetinae
Dexamethasone / pharmacology
Eye Proteins / genetics,  metabolism
Genetic Vectors
Homeodomain Proteins / genetics,  metabolism
Insulin / genetics,  metabolism
Islets of Langerhans / drug effects,  metabolism*,  pathology
Lectins, C-Type / genetics,  metabolism
Membrane Glycoproteins / genetics,  metabolism
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins / genetics,  metabolism
Paired Box Transcription Factors / genetics,  metabolism
RNA, Messenger / metabolism
Rats
Receptor, Epidermal Growth Factor / metabolism
Receptors, Transforming Growth Factor beta / metabolism
Repressor Proteins / genetics,  metabolism*
Trans-Activators / genetics,  metabolism
Transfection
Grant Support
ID/Acronym/Agency:
DK61436/DK/NIDDK NIH HHS; R01 DK061436-06/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Egfr protein, rat; 0/Eye Proteins; 0/Homeodomain Proteins; 0/Insulin; 0/Klrg1 protein, rat; 0/Lectins, C-Type; 0/Membrane Glycoproteins; 0/Nerve Tissue Proteins; 0/Neurog3 protein, rat; 0/Nkx6a protein, rat; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/RNA, Messenger; 0/Receptors, Transforming Growth Factor beta; 0/Repressor Proteins; 0/Trans-Activators; 0/pancreatic and duodenal homeobox 1 protein; 147955-03-1/INSM1 protein, human; 169238-82-8/NeuroD protein; 50-02-2/Dexamethasone; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 3.2.1.-/Amylases
Comments/Corrections

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