PPARγ配体对胃上皮细胞中TFF表达的上调作用。

Up-regulation of TFF expression by PPARgamma ligands in gastric epithelial cells.

作者信息

Shimada T, Koitabashi A, Kuniyoshi T, Hashimoto T, Yoshiura K, Yoneda M, Hiraishi H, Terano A

机构信息

Department of Gastroenterology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.

出版信息

Aliment Pharmacol Ther. 2003 Jul;18 Suppl 1:119-25. doi: 10.1046/j.1365-2036.18.s1.14.x.

DOI:10.1046/j.1365-2036.18.s1.14.x

PMID:12925149

Abstract

BACKGROUND

Although trefoil factor family peptides (TFF peptides) are assumed to play important roles in gastric mucosal protection, the regulatory mechanism of gastric TFF expression has not been fully understood yet. Recent reports showed gastric expression of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor known to be involved in the regulation of cell growth and differentiation in other cell types, such as adipocytes.

AIM

To determine whether PPARgamma affects the expression of TFF in gastric epithelial cells.

METHODS

MKN45 gastric cells were used as a model of gastric epithelial cells. DNA synthesis of the cells was determined by the measurement of BrdU incorporation. The effects of PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) on TFF expression were assessed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS

MKN45 cells expressed a significant amount of PPARgamma. Both 15d-PGJ2 and TGZ suppressed DNA synthesis of the cells in a dose-dependent manner. In the control condition, MKN45 cells most abundantly expressed TFF1 and the relative expression level of TFF1, TFF2, and TFF3 mRNA was 1700:32:1. TFF1 and TFF2 mRNA levels were significantly up-regulated by the incubation of the cells with 15d-PGJ2 (10 micro m) or TGZ (30 micro m), whereas TFF3 mRNA level was not affected.

CONCLUSION

The results of the present study suggest a possible role of PPARgamma in the regulation of TFF expression in gastric epithelial cells.

摘要

背景

尽管三叶因子家族肽（TFF肽）被认为在胃黏膜保护中发挥重要作用，但胃TFF表达的调节机制尚未完全明确。最近的报道显示胃中存在过氧化物酶体增殖物激活受体γ（PPARγ）的表达，PPARγ是一种核受体，已知参与调节其他细胞类型（如脂肪细胞）的细胞生长和分化。

目的

确定PPARγ是否影响胃上皮细胞中TFF的表达。

方法

采用MKN45胃细胞作为胃上皮细胞模型。通过测量BrdU掺入量来测定细胞的DNA合成。采用实时定量逆转录-聚合酶链反应（RT-PCR）评估PPARγ配体15-脱氧-Δ12,14-前列腺素J2（15d-PGJ2）和曲格列酮（TGZ）对TFF表达的影响。

结果

MKN45细胞表达大量的PPARγ。15d-PGJ2和TGZ均以剂量依赖方式抑制细胞的DNA合成。在对照条件下，MKN45细胞中TFF1表达最为丰富，TFF1、TFF2和TFF3 mRNA的相对表达水平为1700:32:1。用15d-PGJ2（10 μmol）或TGZ（30 μmol）孵育细胞后，TFF1和TFF2 mRNA水平显著上调，而TFF3 mRNA水平未受影响。