TGF-α inhibits apoptosis of murine gastric pit cells through an NF-κB-dependent pathway
TGF-α inhibits apoptosis of murine gastric pit cells through an NF-κB-dependent pathway
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DOI：
10.1053/gast.2001.25544
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发表时间：
2001-07-01
期刊：
影响因子：
29.4
通讯作者：
Chiba, T
中科院分区：
文献类型：
--
作者：
Kanai, M;Konda, Y;Chiba, T
背景与目的：近年来，一些生长因子不仅作为生长因子，而且作为细胞存活因子发挥作用。转化生长因子（TGF）-α在正常胃粘膜中表达。本研究探讨了TGF-α对胃粘膜细胞的存活作用及其信号转导机制。方法：我们使用胃粘膜细胞系GSM 06和胃癌细胞系AGS。细胞凋亡诱导血清耗竭或暴露于丁酸钠。通过DNA梯状条带分析、测量DNA片段化率（Burton法）和4 '，6-二脒基-2-苯基吲哚染色进行细胞凋亡分析。结果：TGF-α对血清耗竭或丁酸钠诱导的胃粘膜细胞凋亡具有剂量依赖性保护作用。TGF-α的这种抗凋亡作用可通过用可能抑制NF-κ B活化的试剂预处理来阻断，而MEK抑制剂PD 098059和PI-3-hinase抑制剂渥曼青霉素都不能消除这种作用。电泳迁移率变动分析显示TGF-α刺激可激活核因子κ B（NF-κ B）。TGF-α还以NF-κ B依赖的方式增强Bcl-2家族蛋白的表达。结论：TGF-α通过NF-κ B依赖性途径在胃粘膜细胞中发挥抗凋亡作用。
Background & Aims: Recently, some growth factors have been shown to play roles not only as growth factors but also as cell-surviving factors. Transforming growth factor (TGF)-alpha is expressed in normal gastric mucosa. In this study, we investigated the cell-surviving effect of TGF-alpha on gastric mucosal cells and its signaling mechanism. Methods: We used a gastric mucosal cell line, GSM06, and gastric cancer cell line, AGS. Apoptosis was induced by serum depletion or exposure to sodium butyrate. Analysis of apoptosis was performed by DNA ladder assay, measuring the DNA fragmentation ratio (Burton method), and 4',6-diamidino-2-phenylindole staining. Results: TGF-alpha protected gastric mucosal cells against apoptosis induced by serum depletion or sodium butyrate in a dose-dependent manner. This antiapoptotic effect of TGF-alpha was blocked by the pretreatment with reagents that can potentially inhibit NF-kappaB activation, whereas neither MEK inhibitor PD098059 nor PI-3-hinase inhibitor wortmannin abolished this effect. Electrophoretic mobility shift assay showed nuclear factor kappaB (NF-kappaB) activation by TGF-alpha stimulation. TGF-alpha also enhanced the expression of Bcl-2 family proteins in an NF-kappaB- dependent manner. Conclusions: TGF-alpha plays an antiapoptotic role in gastric mucosal cells via the NF-kappaB-dependent pathway.