科研之友
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摘要
Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1-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-beta 1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D. The cell models of siRNA-mediated silencing of TGF-beta receptor type II (T beta RII), Smad2, Smad3, Smad4, and Smad7 were employed in this study. Our results demonstrate that TGF-beta 1 activates ERK in a time-dependent manner with a maximum effect at 60 min; overexpression of Smad7 increased this TGF-beta 1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of T beta RII, Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-beta 1-mediated ERK phosphorylation in Smad4 knockdown cells but not in T beta RII knockdown cells. In BEP2D cells, TGF-beta 1 treatment effectively inhibited cells' proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly enhanced the TGF-beta 1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that T beta RII and Smad7 play the critical roles in TGF-beta 1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through up-regulating Smad7 expression; and TGF-beta 1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and apoptosis regulation.
