TY - JOUR
T1 - Bombesin enhances TGF-β growth inhibitory effect through apoptosis induction in intestinal epithelial cells
AU - Liu, Xianghua
AU - Zhao, Junmei
AU - Li, Fazhi
AU - Guo, Yan shi
AU - Hellmich, Mark R.
AU - Townsend, Courtney M.
AU - Cao, Yanna
AU - Ko, Tien C.
N1 - Funding Information:
We thank Dr. D. Song for technical support; M. Griffin in Flow Cytometry and Cell Sorting Core Facility, Univ. of Texas Medical Branch for flow cytometric analysis; E. Figueroa and S. Schuenke in the Department of Surgery, Univ. of Texas Medical Branch for manuscript preparation. This study was supported by Public Health Service grants P01 DK035608 (C.M.T. and T.C.K.) and R01 DK060105 (T.C.K.).
PY - 2009/11/27
Y1 - 2009/11/27
N2 - Mammalian intestinal epithelium undergoes continuous cell turn over, with cell proliferation in the crypts and apoptosis in the villus. Both transforming growth factor (TGF)-β 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-β and bombesin (BBS) synergistically induce cyclooxygenase-2 (COX-2) expression and subsequent prostaglandin E2 (PGE2) production through p38MAPK in rat intestinal epithelial cell line stably transfected with GRP receptor (RIE/GRPR), suggesting the interaction between TGF-β signaling pathway and GRPR. The current study examined the biological responses of RIE/GRPR cells to TGF-β and BBS. Treatment with TGF-β1 (40 pM) and BBS (100 nM) together synergistically inhibited RIE/GRPR growth and induced apoptosis. Pretreatment with SB203580 (10 μM), a specific inhibitor of p38MAPK, partially blocked the synergistic effect of TGF-β and BBS on apoptosis. In conclusion, BBS enhanced TGF-β growth inhibitory effect through apoptosis induction, which is at least partially mediated by p38MAPK.
AB - Mammalian intestinal epithelium undergoes continuous cell turn over, with cell proliferation in the crypts and apoptosis in the villus. Both transforming growth factor (TGF)-β 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-β and bombesin (BBS) synergistically induce cyclooxygenase-2 (COX-2) expression and subsequent prostaglandin E2 (PGE2) production through p38MAPK in rat intestinal epithelial cell line stably transfected with GRP receptor (RIE/GRPR), suggesting the interaction between TGF-β signaling pathway and GRPR. The current study examined the biological responses of RIE/GRPR cells to TGF-β and BBS. Treatment with TGF-β1 (40 pM) and BBS (100 nM) together synergistically inhibited RIE/GRPR growth and induced apoptosis. Pretreatment with SB203580 (10 μM), a specific inhibitor of p38MAPK, partially blocked the synergistic effect of TGF-β and BBS on apoptosis. In conclusion, BBS enhanced TGF-β growth inhibitory effect through apoptosis induction, which is at least partially mediated by p38MAPK.
KW - Cell cycle
KW - Gastrin-releasing peptide receptor
KW - p38
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U2 - 10.1016/j.regpep.2009.07.010
DO - 10.1016/j.regpep.2009.07.010
M3 - Article
C2 - 19631696
AN - SCOPUS:70349740790
SN - 0167-0115
VL - 158
SP - 26
EP - 31
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 1-3
ER -