کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2023002 | 1542431 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: RXFP1-inactive relaxin activates human glucocorticoid receptor: Further investigations into the relaxin–GR pathway RXFP1-inactive relaxin activates human glucocorticoid receptor: Further investigations into the relaxin–GR pathway](/preview/png/2023002.png)
The relaxin peptide family regulates diverse biological functions (central nervous processes, reproduction, cardiovascular and kidney function, and connective tissue composition) through different G protein-coupled receptors. We reported earlier that human relaxin-2 and porcine relaxin additionally interact with the human glucocorticoid receptor (GR) in an agonistic manner. Here we investigated whether the membrane receptor RXFP1 is critically involved in this pathway. We used chemically modified porcine relaxin which was biologically inactive at RXFP1. Native porcine relaxin, but not the modified peptide affected RXFP1-dependent and GR-independent readouts: ERK-1/2 and Akt phosphorylation as well as up-regulation of Akt and endothelin type-B receptor. In contrast, relaxin and modified relaxin inhibited endotoxin-stimulated secretion of TNF-α and IL-6 by human macrophages, an effect sensitive to the glucocorticoid receptor antagonists RU-486 and D-06. Both relaxins caused Ser211 phosphorylation of GR, a biomarker of agonist-related receptor activation. Relaxin-induced accumulation of Ser211-phosphorylated GR was found in the cytoplasm and nucleus of HeLa cells, in endothelial cells, and in transfected HT-29 cells. In AP-1-luciferase assays, relaxin and modified relaxin inhibited endotoxin-induced activation of AP-1, a transcription factor essentially involved in endotoxin signaling. This study suggests that the inability of relaxin to interact with its membrane receptor does not interfere with its ability to activate GR.
Journal: Regulatory Peptides - Volume 154, Issues 1–3, 10 April 2009, Pages 77–84