scholarly journals The mineralocorticoid receptor-p38MAPK-NFκB or ERK-Sp1 signal pathways mediate aldosterone-stimulated inflammatory and profibrotic responses in rat vascular smooth muscle cells

2012 ◽  
Vol 33 (7) ◽  
pp. 873-878 ◽  
Author(s):  
Chuan-jiang Zhu ◽  
Qing-qing Wang ◽  
Jun-lan Zhou ◽  
Han-zhi Liu ◽  
Fang Hua ◽  
...  
Author(s):  
Rogelio Salazar-Enciso ◽  
Nohemi A. Camacho-Concha ◽  
Thassio R. Mesquita ◽  
Débora Falcón ◽  
Jean-Pierre Benitah ◽  
...  

2011 ◽  
Vol 89 (9) ◽  
pp. 655-663 ◽  
Author(s):  
Robert Gros ◽  
Qingming Ding ◽  
Mark Davis ◽  
Rasha Shaikh ◽  
Bonan Liu ◽  
...  

It is increasingly appreciated that steroid hormones such as aldosterone and estradiol can mediate important cardiovascular effects. Many of these effects occur over a time course not consistent with the genomic actions of these hormones acting through classical nuclear receptors / transcription factors. Further, multiple receptors have been implicated in mediating these rapid effects of both aldosterone and estradiol, including a newly appreciated G-protein-coupled receptor, GPR30. In previous studies we demonstrated that both aldosterone and estradiol mediate contraction in vascular smooth muscle cells, as assessed in single cell assays. However, the receptor mechanisms underlying these effects remained unclear. Therefore, we studied the actions of estradiol and aldosterone on rat aortic vascular smooth muscle cells. Both aldosterone and estradiol mediated a concentration-dependent increase in contraction, as assessed in substrate deformation assays with EC50s in the range of nanomoles per litre. These effects paralleled increased myosin light chain phosphorylation. The effects of aldosterone were inhibited by the mineralocorticoid selective antagonist eplerenone. Further, aldosterone’s contractile effects were enhanced by increased expression of the mineralocorticoid receptor. The contractile effects of estradiol were inhibited by estrogen receptor (ER)-selective antagonists, tamoxifen, and ICI 182780, as well as eplerenone. Further, estradiol’s effects were enhanced by the increased expression of both ERα and the mineralocorticoid receptor (MR). To assess the potential role of GPR30 in mediating the effects of aldosterone and estradiol, GPR30 was re-introduced, since these cells lose endogenous GPR30 expression in culture. Re-expression of GPR30 enhanced both estradiol- and aldosterone-mediated contraction. These studies demonstrate that in rat aortic vascular smooth muscle cells, both aldosterone and estradiol mediate vascular smooth muscle contraction and that these effects can be mediated by MR, ERα, and by GPR30.


FEBS Letters ◽  
2002 ◽  
Vol 521 (1-3) ◽  
pp. 180-184 ◽  
Author(s):  
Jifeng Zhang ◽  
Mingui Fu ◽  
David Myles ◽  
Xiaojun Zhu ◽  
Jie Du ◽  
...  

2016 ◽  
Vol 30 (4) ◽  
pp. 1610-1622 ◽  
Author(s):  
Maria Bretschneider ◽  
Bianca Busch ◽  
Daniel Mueller ◽  
Alexander Nolze ◽  
Barbara Schreier ◽  
...  

2002 ◽  
Vol 282 (2) ◽  
pp. H784-H792 ◽  
Author(s):  
Mingyan Hou ◽  
T. Kendall Harden ◽  
Cynthia M. Kuhn ◽  
Bo Baldetorp ◽  
Eduardo Lazarowski ◽  
...  

Mitogenic effects of the extracellular nucleotides ATP and UTP are mediated by P2Y1, P2Y2, and P2Y4 receptors. However, it has not been possible to examine the highly expressed UDP-sensitive P2Y6 receptor because of the lack of stable, selective agonists. In rat aorta smooth muscle cells (vascular smooth muscle cells; VSMC), UDP and UTP stimulated 3H-labeled thymidine incorporation with similar pEC50 values (5.96 and 5.69). Addition of hexokinase did not reduce the mitogenic effect of UDP. In cells transfected with P2Y receptors the stable pyrimidine agonist uridine 5'- O-(2-thiodiphosphate) (UDPβS) was specific for P2Y6 with no effect on P2Y1, P2Y2, or P2Y4 receptors. UDPβS stimulated [3H]thymidine and [3H]leucine incorporation and increased cell number in VSMC. Flow cytometry demonstrated that UDP stimulated cell cycle progression to both the S and G2phases. The intracellular signal pathways were dependent on phospholipase C, possibly protein kinase C-δ, and a tyrosine kinase pathway but independent of Gi proteins, eicosanoids, and protein kinase A. The half-life of P2Y6 receptor mRNA was <1 h by competitive RT-PCR. The mitogen-activated protein kinase kinase inhibitor PD-098059 significantly suppressed, whereas ATP and interleukin-1β upregulated, expression of P2Y6 receptor mRNA. The results demonstrate that UDP stimulates mitogenesis through activation of P2Y6 receptors and that the receptor is regulated by factors important in the development of vascular disease.


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