Epac is required for exogenous and endogenous stimulation of adenosine A2B receptor for inhibition of angiotensin II-induced collagen synthesis and myofibroblast differentiation
Autor: | Sarawuth Phosri, Warisara Parichatikanond, Vilasinee Hirunpanich Sato, Kwanchai Bunrukchai, Supachoke Mangmool |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Chemistry Cardiac fibrosis Cell Biology 030204 cardiovascular system & hematology medicine.disease Angiotensin II Adenosine Cell biology 03 medical and health sciences Cellular and Molecular Neuroscience 030104 developmental biology 0302 clinical medicine Fibrosis cardiovascular system medicine Signal transduction Receptor Molecular Biology Myofibroblast Adenosine A2B receptor medicine.drug |
Zdroj: | Purinergic Signalling. 14:141-156 |
ISSN: | 1573-9546 1573-9538 |
Popis: | Angiotensin II (Ang II) plays an important role on the pathogenesis of cardiac fibrosis. Prolong and overstimulation of angiotensin II type 1 receptor with Ang II-induced collagen synthesis and myofibroblast differentiation in cardiac fibroblasts, leading to cardiac fibrosis. Although adenosine and its analogues are known to have cardioprotective effects, the mechanistic by which adenosine A2 receptors (A2Rs) inhibit Ang II-induced cardiac fibrosis is not clearly understood. In the present study, we examined the effects of exogenous adenosine and endogenous adenosine on Ang II-induced collagen and myofibroblast differentiation determined by α-smooth muscle action (α-SMA) overexpression and their underlying signal transduction. Elevation of endogenous adenosine levels resulted in the inhibition of Ang II-induced collagen type I and III and α-SMA synthesis in cardiac fibroblasts. Moreover, treatment with exogenous adenosine which selectively stimulated A2Rs also suppressed Ang II-induced collagen synthesis and α-SMA production. These antifibrotic effects of both endogenous and exogenous adenosines are mediated through the A2B receptor (A2BR) subtype. Stimulation of A2BR exhibited antifibrotic effects via the cAMP-dependent and Epac-dependent pathways. Our results provide new mechanistic insights regarding the role for cAMP and Epac on A2BR-mediated antifibrotic effects. Thus, A2BR is one of the potential therapeutic targets against cardiac fibrosis. |
Databáze: | OpenAIRE |
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