Bencsik, Péter and Kiss, Krisztina and Ágg, Bence and Baán, Júlia Aliz and Ágoston, Gergely and Varga, Albert and Gömöri, Kamilla and Mendler, Luca and Faragó, Nóra and Zvara, Ágnes and Sántha, Péter and Puskás, László and Jancsó, Gábor and Ferdinandy, Péter (2019) Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20 (4). ISSN 1661-6596
|
Text
ijms-20-00991.pdf Download (955kB) | Preview |
Abstract
Here we examined myocardial microRNA (miRNA) expression profile in a sensory neuropathy model with cardiac diastolic dysfunction and aimed to identify key mRNA molecular targets of the differentially expressed miRNAs that may contribute to cardiac dysfunction.Male Wistar rats were treated with vehicle or capsaicin for 3 days to induce systemic sensory neuropathy. Seven days later, diastolic dysfunction was detected by echocardiography, and miRNAs were isolated from the whole ventricles.Out of 711 known miRNAs measured by miRNA microarray, the expression of 257 miRNAs was detected in the heart. As compared to vehicle-treated hearts, miR-344b, miR-466b, miR-98, let-7a, miR-1, miR-206, and miR-34b were downregulated, while miR-181a was upregulated as validated also by quantitative real time polymerase chain reaction (qRT-PCR). By an in silico network analysis, we identified common mRNA targets (insulin-like growth factor 1 (IGF-1), solute carrier family 2 facilitated glucose transporter member 12 (SLC2a-12), eukaryotic translation initiation factor 4e (EIF-4e), and Unc-51 like autophagy activating kinase 2 (ULK-2)) targeted by at least three altered miRNAs. Predicted upregulation of these mRNA targets were validated by qRT-PCR.This is the first demonstration that sensory neuropathy affects cardiac miRNA expression network targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2, which may contribute to cardiac diastolic dysfunction. These results further support the need for unbiased omics approach followed by in silico prediction and validation of molecular targets to reveal novel pathomechanisms.
| Item Type: | Article |
|---|---|
| Additional Information: | Összes idézések száma a WoS-ban: 0 Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Pharmahungary Group, Graphisoft Park, Záhony utca 7, Budapest, H-1031, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Dóm tér 12, Szeged, H-6720, Hungary Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1085, Hungary Heart and Vascular Center, Semmelweis University, Városmajor utca 68, Budapest, H-1122, Hungary Muscle Adaptation Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Institute of Family Medicine, University of Szeged, Tisza Lajos krt. 109, Szeged, H-6720, Hungary Institute of Biochemistry II, Goethe University Medical School, University Hospital Building, 75, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári körút 62, Szeged, H-6726, Hungary Department of Physiology, University of Szeged, Dóm tér 10, Szeged, H-6720, Hungary Cited By :2 Export Date: 22 July 2019 Correspondence Address: Ferdinandy, P.; Pharmahungary Group, Graphisoft Park, Záhony utca 7, Hungary; email: peter.ferdinandy@pharmahungary.com Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Pharmahungary Group, Graphisoft Park, Záhony utca 7, Budapest, H-1031, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Dóm tér 12, Szeged, H-6720, Hungary Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1085, Hungary Heart and Vascular Center, Semmelweis University, Városmajor utca 68, Budapest, H-1122, Hungary Muscle Adaptation Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Institute of Family Medicine, University of Szeged, Tisza Lajos krt. 109, Szeged, H-6720, Hungary Institute of Biochemistry II, Goethe University Medical School, University Hospital Building, 75, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári körút 62, Szeged, H-6726, Hungary Department of Physiology, University of Szeged, Dóm tér 10, Szeged, H-6720, Hungary Cited By :2 Export Date: 23 August 2019 Correspondence Address: Ferdinandy, P.; Pharmahungary Group, Graphisoft Park, Záhony utca 7, Hungary; email: peter.ferdinandy@pharmahungary.com Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Pharmahungary Group, Graphisoft Park, Záhony utca 7, Budapest, H-1031, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Dóm tér 12, Szeged, H-6720, Hungary Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1085, Hungary Heart and Vascular Center, Semmelweis University, Városmajor utca 68, Budapest, H-1122, Hungary Muscle Adaptation Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Institute of Family Medicine, University of Szeged, Tisza Lajos krt. 109, Szeged, H-6720, Hungary Institute of Biochemistry II, Goethe University Medical School, University Hospital Building, 75, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári körút 62, Szeged, H-6726, Hungary Department of Physiology, University of Szeged, Dóm tér 10, Szeged, H-6720, Hungary Cited By :2 Export Date: 24 September 2019 Correspondence Address: Ferdinandy, P.; Pharmahungary Group, Graphisoft Park, Záhony utca 7, Hungary; email: peter.ferdinandy@pharmahungary.com |
| Uncontrolled Keywords: | CAPSAICIN; HEART; sensory neuropathy; microRNA; Network analysis; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 21 Nov 2019 12:42 |
| Last Modified: | 21 Nov 2019 12:42 |
| URI: | http://real.mtak.hu/id/eprint/103498 |
Actions (login required)
 |
Edit Item |
