Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs
by
Péter Bencsik 1,2,3,†, Krisztina Kiss 1,†, Bence Ágg 2,4,5
, Júlia A. Baán 6, Gergely Ágoston 7, Albert Varga 7, Kamilla Gömöri 2,3, Luca Mendler 6,8, Nóra Faragó 9, Ágnes Zvara 9, Péter Sántha 10, László G. Puskás 9, Gábor Jancsó 10 and Péter Ferdinandy 2,4,*
Péter Bencsik 1,2,3,†, Krisztina Kiss 1,†, Bence Ágg 2,4,5, Júlia A. Baán 6, Gergely Ágoston 7, Albert Varga 7, Kamilla Gömöri 2,3, Luca Mendler 6,8, Nóra Faragó 9, Ágnes Zvara 9, Péter Sántha 10, László G. Puskás 9, Gábor Jancsó 10 and Péter Ferdinandy 2,4,*
1
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary
2
Pharmahungary Group, Graphisoft Park, Záhony utca 7, H-1031 Budapest, Hungary
3
Department of Pharmacology and Pharmacotherapy, University of Szeged, Dóm tér 12, H-6720 Szeged, Hungary
4
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, H-1085 Budapest, Hungary
5
Heart and Vascular Center, Semmelweis University, Városmajor utca 68, H-1122 Budapest, Hungary
6
Muscle Adaptation Group, Department of Biochemistry, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary
7
Institute of Family Medicine, University of Szeged, Tisza Lajos krt. 109., H-6720 Szeged, Hungary
8
Institute of Biochemistry II, Goethe University Medical School, University Hospital Building 75, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
9
Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári körút 62, H-6726 Szeged, Hungary
10
Department of Physiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(4), 991; https://doi.org/10.3390/ijms20040991
Received: 10 January 2019 / Revised: 14 February 2019 / Accepted: 19 February 2019 / Published: 25 February 2019
(This article belongs to the Special Issue Novel Molecular Targets for Cardioprotection: The EU-CARDIOPROTECTION COST Action (CA16225))
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
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Keywords:
capsaicin; heart; network analysis; microRNA; sensory neuropathy
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MDPI and ACS Style
Bencsik, P.; Kiss, K.; Ágg, B.; Baán, J.A.; Ágoston, G.; Varga, A.; Gömöri, K.; Mendler, L.; Faragó, N.; Zvara, Á.; Sántha, P.; Puskás, L.G.; Jancsó, G.; Ferdinandy, P. Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs. Int. J. Mol. Sci. 2019, 20, 991.
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