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Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated
Louise Winkel1, Annika Bagge2, Louise Larsen1
1a Department of Biomedical Sciences , University of Copenhagen , Copenhagen , Denmark.
Insights
Trefoil factor 3 (TFF3) peptide promotes pancreatic beta-cell maturation by enhancing cell adhesion and spreading during the critical perinatal period. Gestational low-protein diets alter TFF3 expression, impacting this developmental process.
Area of Science:
- Endocrinology
- Developmental Biology
- Cell Biology
Background:
- The endocrine pancreas undergoes significant expansion and functional maturation of beta-cells postnatally.
- Trefoil factor 3 (TFF3), known for intestinal epithelial roles, has an uncharacterized function in pancreatic development.
Purpose of the Study:
- To investigate the expression and functional role of TFF3 in perinatal rat pancreas development.
- To explore TFF3's impact on beta-cell maturation and its modulation by gestational nutrition.
Main Methods:
- Analysis of TFF3 mRNA and protein expression in perinatal rat pancreas under control and low-protein diet conditions.
- In vitro studies using INS-1E beta-cell line and ex vivo cultured fetal rat pancreas to assess TFF3 function.
- Investigated TFF3's effects on cell adhesion, spreading, EGFR phosphorylation, insulin mRNA, and Pref1/Dlk1 expression.
Main Results:
- TFF3 mRNA expression peaked at postnatal day 0 (P0) and was further upregulated in pups from protein-undernourished mothers.
- TFF3 enhanced INS-1E beta-cell attachment, spreading, and EGFR phosphorylation.
- Ex vivo cultured pancreas showed TFF3 increased cellular spreading, insulin mRNA, and Pref1/Dlk1 expression.
Conclusions:
- TFF3 plays a functional role in promoting pancreatic beta-cell maturation by enhancing cell adhesion and spreading.
- Gestational low-protein diet significantly alters TFF3 expression and potentially impacts perinatal beta-cell development.
Abstract:
The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E. Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3. These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.
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