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Autocrine and paracrine transcriptional regulation of type IIA secretory phospholipase A2 gene in vascular smooth muscle cells.

AbstractOBJECTIVE:
The inflammation that occurs during the development of atherosclerosis is characterized by a massive release of sPLA2-IIA (group IIA secretory phospholipase A2) from vascular smooth muscle cells (VSMCs). We have investigated the autocrine function of sPLA2-IIA in rat aortic and human VSMCs.
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.
AuthorsAmandine Jaulmes, Brigitte Janvier, Marise Andreani, Michel Raymondjean
JournalArteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 25 Issue 6 Pg. 1161-7 (Jun 2005) ISSN: 1524-4636 [Electronic] United States
PMID15802623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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