Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Line
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Humans
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Lung / cytology
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Lung / drug effects*
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Lung / metabolism
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Mice
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Smad2 Protein
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Smad3 Protein
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transforming Growth Factor beta / pharmacology*
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A / biosynthesis*
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Vascular Endothelial Growth Factor A / metabolism
Substances
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DNA-Binding Proteins
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RNA, Small Interfering
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SMAD2 protein, human
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SMAD3 protein, human
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Smad2 Protein
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Smad2 protein, mouse
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Smad3 Protein
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Smad3 protein, mouse
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TGFB1 protein, human
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Tgfb1 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A