The stellate vascular smooth muscle cell phenotype is induced by IL-1β via the secretion of PGE2 and subsequent cAMP-dependent protein kinase A activation - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Biochimica et Biophysica Acta - Molecular Cell Research Année : 2015

The stellate vascular smooth muscle cell phenotype is induced by IL-1β via the secretion of PGE2 and subsequent cAMP-dependent protein kinase A activation

Résumé

Atherosclerosis development is associated with morphological changes to intimal cells, leading to a stellate cell phenotype. In this study, we aimed to determine whether and how key pro-atherogenic cytokines present in atherosclerotic plaques (IL-1β, TNFα and IFNγ) could induce this phenotype, as these molecules are known to trigger the transdifferentiation of vascular smooth muscle cells (VSMCs). We found that, IL-1β was the only major inflammatory mediator tested capable of inducing a stellate morphology in VSMCs. This finding was confirmed by staining for F-actin and vinculin at focal adhesions, as these two markers were disrupted only by IL-1β. We then investigated the possible association of this IL-1β-dependent change in morphology with an increase in intracellular cAMP concentration ([cAMP]), using the FRET-based biosensor for cAMP TEpacVV. Experiments in the presence of IL-1β or medium conditioned by IL-1β-treated VSMCs and pharmacological tools demonstrated that the long-term increase in intracellular cAMP concentration was induced by the secretion of an autocrine/paracrine mediator, prostaglandin E2 (PGE2), acting through the EP4 receptor. Finally, by knocking down the expression of the regulatory subunit PKAR1α, thereby reproducing the effects of IL-1β and PGE2 on VSMCs, we demonstrated the contribution of PKA activity to the observed behavior of VSMCs.
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Dates et versions

hal-01217160 , version 1 (19-10-2015)

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Karl Blirando, Régis Blaise, Natalia Gorodnaya, Clotilde Rouxel, Olivier Meilhac, et al.. The stellate vascular smooth muscle cell phenotype is induced by IL-1β via the secretion of PGE2 and subsequent cAMP-dependent protein kinase A activation. Biochimica et Biophysica Acta - Molecular Cell Research, 2015, 1853 (12), pp.3235-3247. ⟨10.1016/j.bbamcr.2015.09.019⟩. ⟨hal-01217160⟩
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