Abstract | OBJECTIVE: METHODS AND RESULTS: We found that the transcription of the endogenous sPLA2-IIA gene increased by adding a cell supernatant containing human sPLA2-IIA proteins. We show that this effect was independent of the sPLA2 activity using sPLA2-IIA proteins lacking enzyme activity. Transient transfections with various sPLA2-IIA rat promoter- luciferase constructs demonstrated that the C/EBP, NK-kappaB, and Ets transcription factors are involved in the increase in sPLA2-IIA gene transcription. We also found the M-type sPLA2 receptor mRNA in VSMCs, and we showed that the sPLA2-luciferase reporter gene was induced by the specific agonist of the sPLA2 receptor, aminophenylmannopyranoside (APMP), and that this induction was mediated by the same transcription factor-binding sites. Finally, we used a sPLA2-IIA mutant unable to bind heparan-sulfate proteoglycans to show that the binding of wild-type sPLA2-IIA to proteoglycans is essential for the induction of an autocrine loop. CONCLUSIONS: We have thus identified new autocrine and paracrine pathways activating sPLA2-IIA gene expression in rat and human VSMCs.
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Authors | Amandine Jaulmes, Brigitte Janvier, Marise Andreani, Michel Raymondjean |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 25
Issue 6
Pg. 1161-7
(Jun 2005)
ISSN: 1524-4636 [Electronic] United States |
PMID | 15802623
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CCAAT-Enhancer-Binding Proteins
- NF-kappa B
- PLA2R1 protein, human
- Proteoglycans
- Receptors, Cell Surface
- Receptors, Phospholipase A2
- Winged-Helix Transcription Factors
- Phospholipases A
- Group II Phospholipases A2
- Phospholipases A2
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Topics |
- Animals
- Aorta, Thoracic
(cytology)
- Autocrine Communication
(physiology)
- CCAAT-Enhancer-Binding Proteins
(metabolism)
- Cells, Cultured
- Gene Expression Regulation, Enzymologic
(physiology)
- Group II Phospholipases A2
- Humans
- Male
- Muscle, Smooth, Vascular
(cytology, enzymology)
- NF-kappa B
(metabolism)
- Paracrine Communication
(physiology)
- Phospholipases A
(genetics, metabolism)
- Phospholipases A2
- Protein Binding
- Proteoglycans
(metabolism)
- Rats
- Rats, Wistar
- Receptors, Cell Surface
(genetics, metabolism)
- Receptors, Phospholipase A2
- Transcriptional Activation
(physiology)
- Winged-Helix Transcription Factors
(metabolism)
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