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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gammeltoft, Steen Nossent, Anne Yaël Schneider, Mikael Jensen, Hasse Brønnum Andersen, Ditte Caroline Christensen, Gitte Lund Sheikh, Søren Paludan Eskildsen, Tilde Jeppesen, Pia Lindgren Hansen, Jakob Lerche |
| Description | Author Affiliation: Jeppesen PL ( Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark and Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense, Denmark.) |
| Abstract | BACKGROUND AND PURPOSE: The angiotensin II type 1 receptor (AT(1)R) is a key regulator of blood pressure and cardiac contractility and is profoundly involved in development of cardiac disease. Since several microRNAs (miRNAs) have been implicated in cardiac disease, we determined whether miRNAs might be regulated by AT(1)R signals in a G q/11-dependent or -independent manner. EXPERIMENTAL APPROACH: We performed a global miRNA array analysis of angiotensin II (Ang II)-mediated miRNA regulation in HEK293N cells overexpressing the AT(1)R and focused on separating the role of G q/11-dependent and -independent pathways. MiRNA regulation was verified with quantitative PCR in both HEK293N cells and primary cardiac myocytes and fibroblasts. KEY RESULTS: Our studies revealed five miRNAs (miR-29b, -129-3p, -132, -132* and -212) that were up-regulated by Ang II in HEK293N cells. In contrast, the biased Ang II analogue, [Sar1, Ile4, Ile8] Ang II (SII Ang II), which selectively activates G q/11-independent signalling, failed to regulate miRNAs in HEK293N cells. Furthermore, Ang II-induced miRNA regulation was blocked following G q/11 and Mek1 inhibition. The observed Ang II regulation of miRNA was confirmed in primary cultures of adult cardiac fibroblasts. Interestingly, Ang II did not regulate miRNA expression in cardiac myocytes, but SII Ang II significantly down-regulated miR-129-3p. CONCLUSIONS AND IMPLICATIONS: Five miRNAs were regulated by Ang II through mechanisms depending on G q/11 and Erk1/2 activation. These miRNAs may be involved in Ang II-mediated cardiac biology and disease, as several of these miRNAs have previously been associated with cardiovascular disease and were found to be regulated in cardiac cells. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 164 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2011-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Fibroblasts Physiology Gene Expression Regulation MicroRNAs Metabolism Myocytes, Cardiac Receptor, Angiotensin, Type 1 Angiotensin II Pharmacology Anthracenes Butadienes Extracellular Signal-Regulated MAP Kinases Genetics GTP-Binding Protein Alpha Subunits, Gq-G11 Gene Expression Profiling HEK293 Cells Imidazoles Nitriles Pyridines Signal Transduction Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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