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.

产后第一天内分泌胰腺明显扩张，产生胰岛素的β细胞开始功能成熟，随后朗格汉斯岛的形态发生变化。三叶因子3（TFF3）是在肠上皮细胞中表达的一种分泌肽，在其中促进迁移，但尚无其在胰腺中的作用。这项研究的目的是检查TFF3在围产期大鼠胰腺，离体培养的胎鼠胰腺以及大鼠β细胞系INS-1E中的表达和功能。

在胚胎第20天（E20），出生日（P0）和出生后第2天（P2）收获对照组或妊娠期低蛋白饮食的围产期大鼠胰腺。TFF3 mRNA在P0相对于E20上调了4.5倍，在P2再次下调。在蛋白质营养不良的幼崽中，P0处的TFF3诱导进一步增加至9.7倍，并在P2处增加。TFF3引起INS-1Eβ细胞中EGFR的酪氨酸磷酸化，纯化的重组TFF3增加了INS-1Eβ细胞的附着和扩散。在胶原酶消化的胎儿大鼠胰腺的离体培养物中，这是围产期β细胞成熟的模型，TFF3增加细胞扩散以及胰岛素mRNA水平。TFF3还增加了Pref1 / Dlk1的表达，其表达和调控与TFF3相似。

这些结果表明，TFF3可以促进细胞的粘附和扩散以加速β细胞的成熟。这项研究表明，TFF3在围产期胰腺β细胞成熟中具有功能性作用，这种作用在妊娠期间的低蛋白饮食会改变。