The linker region of Smad2 mediates TGF-beta-dependent ERK2-induced collagen synthesis.
Transforming growth factor (TGF)-beta1 can cause fibrosis diseases by enhancing production of collagen. However, the intracellular signaling mechanism for TGF-beta1 stimulation of this process has not been fully elucidated. The present study focused on this mechanism and the cross-talk between the MAPK and Smad pathways. Extracellular signal-regulated kinase (ERK)2 ablation by a small interfering RNA led to marked inhibition of TGF-beta1-induced collagen synthesis and enhanced phosphorylation of the Smad2 linker site in NIH/3T3 fibroblast cells. However, ERK1 ablation had minimal effects. Ablation of either ERK2 or ERK1 had no effect on the phosphorylation of the Smad2 C-terminal site. Furthermore, a Smad2 mutant with reduced phosphorylation of the Smad2 linker site inhibited TGF-beta1-induced collagen synthesis. These results indicate that ERK2, rather than ERK1, plays a predominantly positive role in TGF-beta1-induced collagen synthesis, and that ERK2 enhances collagen synthesis, at least partially, through activation of the Smad2 linker site.
Li
Fengfeng
F
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233, China.
Zeng
Bingfang
B
Chai
Yimin
Y
Cai
Peihua
P
Fan
Cunyi
C
Cheng
Tao
T
D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009154:Mutation; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D024042:Collagen Type I; D024061:Collagen Type III; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3