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Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells.
Cell Biol Toxicol. 2007 Mar; 23(2):113-28.CB

Abstract

Transforming growth factor-beta1 (TGF-beta1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The mechanism of this activation is not well elucidated. Here, we explore the role of TGF-beta/Smads signaling compounds in TGF-beta1-mediated activation of extracellular signal-regulated kinase (ERK) MAPK in human papillomavirus (HPV)-18 immortalized human bronchial epithelial cell line BEP2D and the role of TGF-beta1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D. The cell models of siRNA-mediated silencing of TGF-beta receptor type II (TbetaRII), Smad2, Smad3, Smad4, and Smad7 were employed in this study. Our results demonstrate that TGF-beta1 activates ERK in a time-dependent manner with a maximum effect at 60 min; overexpression of Smad7 increased this TGF-beta1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of TbetaRII, Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-beta1-mediated ERK phosphorylation in Smad4 knockdown cells but not in TbetaRII knockdown cells. In BEP2D cells, TGF-beta1 treatment effectively inhibited cells' proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly enhanced the TGF-beta1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that TbetaRII and Smad7 play the critical roles in TGF-beta1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through up-regulating Smad7 expression; and TGF-beta1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and apoptosis regulation.

Authors+Show Affiliations

Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing, 100850, PR China. yanying_huo@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17096210

Citation

Huo, Y-Y, et al. "Activation of Extracellular Signal-regulated Kinase By TGF-beta1 Via TbetaRII and Smad7 Dependent Mechanisms in Human Bronchial Epithelial BEP2D Cells." Cell Biology and Toxicology, vol. 23, no. 2, 2007, pp. 113-28.
Huo YY, Hu YC, He XR, et al. Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells. Cell Biol Toxicol. 2007;23(2):113-28.
Huo, Y. Y., Hu, Y. C., He, X. R., Wang, Y., Song, B. Q., Zhou, P. K., Zhu, M. X., Li, G., & Wu, D. C. (2007). Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells. Cell Biology and Toxicology, 23(2), 113-28.
Huo YY, et al. Activation of Extracellular Signal-regulated Kinase By TGF-beta1 Via TbetaRII and Smad7 Dependent Mechanisms in Human Bronchial Epithelial BEP2D Cells. Cell Biol Toxicol. 2007;23(2):113-28. PubMed PMID: 17096210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells. AU - Huo,Y-Y, AU - Hu,Y-C, AU - He,X-R, AU - Wang,Y, AU - Song,B-Q, AU - Zhou,P-K, AU - Zhu,M-X, AU - Li,G, AU - Wu,D-C, Y1 - 2006/11/09/ PY - 2006/02/17/received PY - 2006/09/13/accepted PY - 2006/11/11/pubmed PY - 2007/10/12/medline PY - 2006/11/11/entrez SP - 113 EP - 28 JF - Cell biology and toxicology JO - Cell Biol Toxicol VL - 23 IS - 2 N2 - Transforming growth factor-beta1 (TGF-beta1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The mechanism of this activation is not well elucidated. Here, we explore the role of TGF-beta/Smads signaling compounds in TGF-beta1-mediated activation of extracellular signal-regulated kinase (ERK) MAPK in human papillomavirus (HPV)-18 immortalized human bronchial epithelial cell line BEP2D and the role of TGF-beta1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D. The cell models of siRNA-mediated silencing of TGF-beta receptor type II (TbetaRII), Smad2, Smad3, Smad4, and Smad7 were employed in this study. Our results demonstrate that TGF-beta1 activates ERK in a time-dependent manner with a maximum effect at 60 min; overexpression of Smad7 increased this TGF-beta1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of TbetaRII, Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-beta1-mediated ERK phosphorylation in Smad4 knockdown cells but not in TbetaRII knockdown cells. In BEP2D cells, TGF-beta1 treatment effectively inhibited cells' proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly enhanced the TGF-beta1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that TbetaRII and Smad7 play the critical roles in TGF-beta1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through up-regulating Smad7 expression; and TGF-beta1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and apoptosis regulation. SN - 0742-2091 UR - https://www.unboundmedicine.com/medline/citation/17096210/Activation_of_extracellular_signal_regulated_kinase_by_TGF_beta1_via_TbetaRII_and_Smad7_dependent_mechanisms_in_human_bronchial_epithelial_BEP2D_cells_ DB - PRIME DP - Unbound Medicine ER -