TY - JOUR

T1 - Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated beta-cell maturation

AU - Winkel, Louise

AU - Bagge, Annika

AU - Larsen, Louise

AU - Haase, Tobias N.

AU - Rasmussen, Morten

AU - Lykke, Jeanette

AU - Holmgaard, Dennis B.

AU - Thim, Lars

AU - Nielsen, Jens H.

AU - Dalgaard, Louise T.

PY - 2018

Y1 - 2018

N2 - The endocrine pancreas expands markedly in the first postnatal days and the insulin producing -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 -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 P0vs. 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 -cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E -cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal -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 -cell maturation. This study indicates a functional role for TFF3 in pancreatic -cell maturation in the perinatal period, which is altered by low protein diet during gestation.

AB - The endocrine pancreas expands markedly in the first postnatal days and the insulin producing -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 -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 P0vs. 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 -cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E -cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal -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 -cell maturation. This study indicates a functional role for TFF3 in pancreatic -cell maturation in the perinatal period, which is altered by low protein diet during gestation.

KW - adhesion

KW - EGFR

KW - insulin

KW - islets of Langerhans

KW - maturation

KW - perinatal pancreas

KW - Pref1/Dlk1

KW - TFF3 (ITF)

KW - beta-catenin

U2 - 10.1080/19382014.2018.1472186

DO - 10.1080/19382014.2018.1472186

M3 - Journal article

C2 - 29723130

VL - 10

SP - 124

EP - 135

JO - Islets

JF - Islets

SN - 1938-2014

IS - 3

ER -