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cAMP inhibits TGFbeta1-induced in vitro angiogenesis
Beatriz del Valle-Pérez1, Ofelia Maria Martínez-Estrada, Senén Vilaró
1Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fiològiques II, Campus de Bellvitge, Universitat de Barcelona, C/ Feixa Llarga s/n, E-08907 L'Hospitalet de Llobregat, Spain.
FEBS Letters
|July 1, 2004
Summary
Cyclic AMP (cAMP) signaling inhibits transforming growth factor-beta 1 (TGFbeta1)-induced angiogenesis by blocking Smad transcriptional activity. This finding reveals a novel mechanism regulating blood vessel formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Angiogenesis Research
Background:
- Transforming growth factor-beta 1 (TGFbeta1) is a key regulator of angiogenesis, particularly in later stages.
- The precise molecular mechanisms by which TGFbeta1 promotes angiogenesis are complex and still under investigation.
Purpose of the Study:
- To identify genes and pathways involved in TGFbeta1-induced angiogenesis.
- To investigate the role of cyclic AMP (cAMP) in modulating TGFbeta1 signaling and angiogenesis.
Main Methods:
- Down-regulation of adenylate cyclase VI by TGFbeta1 was observed.
- Effects of cAMP analogs and forskolin on TGFbeta1-induced angiogenesis in endothelial cells were assessed.
- Transcriptional activity, Smad phosphorylation, and DNA binding were analyzed.
Main Results:
- cAMP agonists and adenylate cyclase activators reduced TGFbeta1-induced in vitro angiogenesis.
- TGFbeta1-induced expression of Ets-1 and plasminogen activator inhibitor-1 (PAI-1) was blocked by cAMP.
- cAMP inhibited the transcriptional activity of Smads without affecting Smad phosphorylation or nuclear translocation.
Conclusions:
- The cAMP pathway acts as an inhibitor of TGFbeta1-induced angiogenesis.
- cAMP interferes with the transcriptional activity of Smads, mediating the observed anti-angiogenic effect.
- This study elucidates a novel regulatory mechanism in angiogenesis involving the interplay between TGFbeta1 and cAMP signaling.