Smad3 mediates TGF-beta1 induction of VEGF production in lung fibroblasts.
Transforming growth factor-beta1 (TGF-beta1) is a key factor in a variety of physiological and pathological processes. Vascular endothelial growth factor (VEGF) is a key angiogenic factor, and vascular change is one of the features of airway remodeling. We examined the effect of TGF-beta1 on VEGF production by fibroblasts from mice lacking expression of Smad2 or Smad3 as well as human lung fibroblasts treated with or without Smad2 or Smad3 siRNA. TGF-beta1 stimulated VEGF production by fibroblasts from Smad2 deficient animals and wildtype animals. In contrast, TGF-beta1 did not affect VEGF production by fibroblasts from Samd3 deficient mice. Similarly, TGF-beta1 failed to stimulate VEGF production by HFL-1 cells treated with Samd3 siRNA but significantly increased VEGF production by the cells treated with Smad2 siRNA. These result suggest that TGF-beta1 stimulation of VEGF production by fibroblasts is regulated by Smad3 but not by Smad2 signaling.
Kobayashi
Tetsu
T
University of Nebraska Medical Center, Omaha, NE, USA.
Liu
Xiangde
X
Wen
Fu-Qiang
FQ
Fang
Qiuhong
Q
Abe
Shinji
S
Wang
Xiang Qi
XQ
Hashimoto
Mitsuyoshi
M
Shen
Lei
L
Kawasaki
Shin
S
Kim
Hui Jung
HJ
Kohyama
Tadashi
T
Rennard
Stephen I
SI
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A