Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated beta-cell maturation
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Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated beta-cell maturation. / Winkel, Louise; Bagge, Annika; Larsen, Louise; Haase, Tobias N.; Rasmussen, Morten; Lykke, Jeanette; Holmgaard, Dennis B.; Thim, Lars; Nielsen, Jens H.; Dalgaard, Louise T.
I: Islets, Bind 10, Nr. 3, 2018, s. 124–135.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 214404622