- Title
- Contribution of microRNA to pathological fibrosis in cardiorenal syndrome : Impact of uremic toxins
- Creator
- Rana, Indrajeetsinh; Kompa, Andrew; Skommer, Joanna; Wang, Bing; Lekawanvijit, Suree; Kelly, Darren; Krum, Henry; Charchar, Fadi
- Date
- 2015
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/154250
- Identifier
- vital:11075
- Identifier
-
https://doi.org/10.14814/phy2.12371
- Identifier
- ISSN:2051817X
- Abstract
- Progressive reduction in kidney function in patients following myocardial infarction (MI) is associated with an increase in circulating uremic toxins levels leading to increased extracellular matrix deposition. We have recently reported that treatment with uremic toxin adsorbent AST-120 in rats with MI inhibits serum levels of uremic toxin indoxyl sulfate (IS) and downregulates expression of cardiac profibrotic cytokine transforming growth factor beta (TGF-β1). In this study, we examined the effect of uremic toxins post-MI on cardiac microRNA-21 and microRNA-29b expression, and also the regulation of target genes and matrix remodeling proteins involved in TGFβ1 and angiotensin II signaling pathways. Sixteen weeks after MI, cardiac tissues were assessed for pathological and molecular changes. The percentage area of cardiac fibrosis was 4.67 ± 0.17 in vehicle-treated MI, 2.9 ± 0.26 in sham, and 3.32 ± 0.38 in AST-120-treated MI, group of rats. Compared to sham group, we found a twofold increase in the cardiac expression of microRNA-21 and 0.5-fold decrease in microRNA-29b in heart tissue from vehicle-treated MI. Treatment with AST-120 lowered serum IS levels and attenuated both, cardiac fibrosis and changes in expression of these microRNAs observed after MI. We also found increased mRNA expression of angiotensin-converting enzyme (ACE) and angiotensin receptor 1a (Agtr1a) in cardiac tissue collected from MI rats. Treatment with AST-120 attenuated both, expression of ACE and Agtr1a mRNA. Exposure of rat cardiac fibroblasts to IS upregulated angiotensin II signaling and altered the expression of both microRNA-21 and micro- RNA-29b. These results collectively suggest a clear role of IS in altering microRNA-21 and microRNA-29b in MI heart, via a mechanism involving angiotensin signaling pathway, which leads to cardiac fibrosis. © 2015 The Authors.
- Publisher
- American Physiological Society
- Relation
- Physiological Reports Vol. 3, no. 4 (2015), p. 1-15
- Rights
- Copyright © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Rights
- Open Access
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- This metadata is freely available under a CCO license
- Subject
- AST-120; Indoxyl sulfate; microRNA 21; microRNA 29b; Myocardial infarction; Uremic toxin
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