Adenosine A(2A) receptor activation reverses hypoxiainduced rat pulmonary artery smooth muscle cell proliferation via cyclic AMPmediated inhibition of the SDF1CXC4 signaling pathway.
Int J Mol Med
; 42(1): 607-614, 2018 Jul.
Article
en En
| MEDLINE
| ID: mdl-29693117
ABSTRACT
The occurrence and the subsequent development of pulmonary arterial hypertension (PAH) involve complicated mechanisms. Of these, the proliferation of pulmonary artery smooth muscle cells (PASMCs) has been indicated to be closely associated with its progression. Therefore, therapeutic methods targeting PASMCs to inhibit proliferation is an effective method for alleviating PAH. The present study was designed to determine the role of the adenosine A(2A) receptor (A2A receptor) in hypoxiainduced rat PASMC (RPASMC) proliferation. Primary RPASMCs were isolated from the pulmonary artery of adult male SD rats, cultured and used for the following experiments. The mRNA level and protein expression of CXCR4 were measured by reverse transcriptionquantitative polymerase chain reaction and western blot analysis, respectively. The cell proliferation of RPASMCs was measured using a cell proliferation assay kit. In the present study, it was demonstrated that the proliferation of RPASMCs was partially mediated by activation of the stromal cellderived factor 1 (SDF1)CXC chemokine receptor 4 (CXCR4) axis under hypoxic conditions. In addition, SDF1α alone upregulated the mRNA and protein expression levels of CXCR4, and stimulated the proliferation of RPASMCs. The protein expression of CXCR4 and the cell proliferation were markedly inhibited by application of A2A receptor agonist CGS21680 or cyclic adenosine monophosphate (cAMP) under hypoxic conditions or treatment with SDF1α and was reversed by the A2A receptor antagonist SCH58261 or 8bromoadenosine3',5'cyclic monophosphorothioate. These results demonstrated that the inhibition of SDF1CXC4 signaling by the activation of A2A receptor and subsequent increase in the level of cAMP may be a potential method to ameliorate PAH.
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1
Banco de datos:
MEDLINE
Asunto principal:
Arteria Pulmonar
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Transducción de Señal
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AMP Cíclico
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Receptores CXCR4
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Miocitos del Músculo Liso
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Receptor de Adenosina A2A
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Quimiocina CXCL12
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article