Liu Xianghua, Zhao Junmei, Li Fazhi, Guo Yan-shi, Hellmich Mark R, Townsend Courtney M, Cao Yanna, Ko Tien C
Department of Surgery, University of Texas Health Science Center, Houston, Texas 77030, USA.
Regul Pept. 2009 Nov 27;158(1-3):26-31. doi: 10.1016/j.regpep.2009.07.010. Epub 2009 Jul 23.
Mammalian intestinal epithelium undergoes continuous cell turn over, with cell proliferation in the crypts and apoptosis in the villus. Both transforming growth factor (TGF)-beta and gastrin-releasing peptide (GRP) are involved in the regulation of intestinal epithelial cells for division, differentiation, adhesion, migration and death. Previously, we have shown that TGF-beta and bombesin (BBS) synergistically induce cyclooxygenase-2 (COX-2) expression and subsequent prostaglandin E(2) (PGE2) production through p38(MAPK) in rat intestinal epithelial cell line stably transfected with GRP receptor (RIE/GRPR), suggesting the interaction between TGF-beta signaling pathway and GRPR. The current study examined the biological responses of RIE/GRPR cells to TGF-beta and BBS. Treatment with TGF-beta1 (40 pM) and BBS (100 nM) together synergistically inhibited RIE/GRPR growth and induced apoptosis. Pretreatment with SB203580 (10 microM), a specific inhibitor of p38(MAPK), partially blocked the synergistic effect of TGF-beta and BBS on apoptosis. In conclusion, BBS enhanced TGF-beta growth inhibitory effect through apoptosis induction, which is at least partially mediated by p38(MAPK).
哺乳动物的肠上皮细胞经历持续的细胞更新，隐窝处有细胞增殖，绒毛处有细胞凋亡。转化生长因子（TGF）-β和胃泌素释放肽（GRP）都参与肠上皮细胞的分裂、分化、黏附、迁移和死亡的调节。此前，我们已表明，在稳定转染GRP受体（RIE/GRPR）的大鼠肠上皮细胞系中，TGF-β和蛙皮素（BBS）通过p38丝裂原活化蛋白激酶（p38(MAPK)）协同诱导环氧合酶-2（COX-2）表达及随后的前列腺素E2（PGE2）生成，提示TGF-β信号通路与GRPR之间存在相互作用。本研究检测了RIE/GRPR细胞对TGF-β和BBS的生物学反应。用TGF-β1（40 pM）和BBS（100 nM）共同处理可协同抑制RIE/GRPR生长并诱导凋亡。用p38(MAPK)的特异性抑制剂SB203580（10 μM）预处理可部分阻断TGF-β和BBS对凋亡的协同作用。总之，BBS通过诱导凋亡增强了TGF-β的生长抑制作用，这至少部分由p38(MAPK)介导。
