Myt3 Mediates Laminin-V/Integrin-ß1-Induced Islet-Cell Migration via Tgfbi.
Mol Endocrinol
; 29(9): 1254-68, 2015 Sep.
Article
in En
| MEDLINE
| ID: mdl-26177052
ABSTRACT
Myt3 is a prosurvival factor in pancreatic islets; however, its role in islet-cell development is not known. Here, we demonstrate that myelin transcription factor 3 (Myt3) is expressed in migrating islet cells in the developing and neonatal pancreas and thus sought to determine whether Myt3 plays a role in this process. Using an ex vivo model of islet-cell migration, we demonstrate that Myt3 suppression significantly inhibits laminin-V/integrin-ß1-dependent α- and ß-cell migration onto 804G, and impaired 804G-induced F-actin and E-cadherin redistribution. Exposure of islets to proinflammatory cytokines, which suppress Myt3 expression, had a similar effect, whereas Myt3 overexpression partially rescued the migratory ability of the islet cells. We show that loss of islet-cell migration, due to Myt3 suppression or cytokine exposure, is independent of effects on islet-cell survival or proliferation. Myt3 suppression also had no effect on glucose-induced calcium influx, F-actin remodeling or insulin secretion by ß-cells. RNA-sequencing (RNA-seq) analysis of transduced islets showed that Myt3 suppression results in the up-regulation of Tgfbi, a secreted diabetogenic factor thought to impair cellular adhesion. Exposure of islets to exogenous transforming growth factor ß-induced (Tgfbi) impaired islet-cell migration similar to Myt3 suppression. Taken together, these data suggest a model by which cytokine-induced Myt3 suppression leads to Tgfbi de-repression and subsequently to impaired islet-cell migration, revealing a novel role for Myt3 in regulating islet-cell migration.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Cell Adhesion Molecules
/
Cell Movement
/
Integrin beta1
/
Insulin-Secreting Cells
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Endocrinol
Journal subject:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Year:
2015
Document type:
Article