Back to Search
Start Over
FHL1 and Smad4 synergistically inhibit vascular endothelial growth factor expression.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2013 Feb; Vol. 7 (2), pp. 649-53. Date of Electronic Publication: 2012 Nov 26. - Publication Year :
- 2013
-
Abstract
- Vascular endothelial growth factor (VEGF) plays an important role in many disease states, including ischemia, chronic and acute inflammation, and pathologies associated with angiogenesis such as tumors and wounds. A number of factors regulate VEGF promoter activity and VEGF expression such as four and a half LIM domains 1 (FHL1) and Smad4. FHL1 belongs to a family of LIM-only proteins that regulate gene transcription, cell proliferation, differentiation and apoptosis. Smad4 is a tumor suppressor gene, initially identified as deleted in pancreatic carcinoma locus 4 (DPC4). The aim of this study was to determine whether FHL1 and Smad4 inhibited VEGF signaling. HepG2 cells were transfected with the VEGF-Luc reporter, Smad4 and FHL1 or Smad4 and FHL1 siRNA. Results showed that the overexpression of FHL1 and Smad4 synergistically inhibited the promoter activity, mRNA expression and secretion of VEGF, whereas knockdown of endogenous Smad4 and FHL1 had opposite effects. Moreover, the reduction of endogenous Smad4 eliminated FHL1-mediated inhibition of the VEGF promoter activity. In conclusion, a cooperative regulation of VEGF signaling by FHL1 and Smad4 was evidenced, which may provide a novel regulation mechanism underlying cancer development and progression.
- Subjects :
- Gene Expression
HEK293 Cells
Hep G2 Cells
Humans
Intracellular Signaling Peptides and Proteins antagonists & inhibitors
Intracellular Signaling Peptides and Proteins genetics
LIM Domain Proteins antagonists & inhibitors
LIM Domain Proteins genetics
Muscle Proteins antagonists & inhibitors
Muscle Proteins genetics
Promoter Regions, Genetic
RNA Interference
RNA, Small Interfering metabolism
Signal Transduction
Smad4 Protein antagonists & inhibitors
Smad4 Protein genetics
Vascular Endothelial Growth Factor A genetics
Intracellular Signaling Peptides and Proteins metabolism
LIM Domain Proteins metabolism
Muscle Proteins metabolism
Smad4 Protein metabolism
Vascular Endothelial Growth Factor A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 23184087
- Full Text :
- https://doi.org/10.3892/mmr.2012.1202