TY  - JOUR
A1  - Bencsik, Péter
A1  - Kiss, Krisztina
A1  - Ágg, Bence
A1  - Baán, Júlia A.
A1  - Agoston, Gergely
A1  - Varga, Albert
A1  - Gömöri, Kamilla
A1  - Mendler, Luca
A1  - Faragó, Nóra
A1  - Zvara, Ágnes
A1  - Sántha, Péter
A1  - Puskás, László G.
A1  - Jancsó, Gábor
A1  - Ferdinandy, Peter
T1  - Sensory neuropathy affects cardiac miRNA expression network targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs
T2  - International journal of molecular sciences
N2  - 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.
KW  - capsaicin
KW  - heart
KW  - network analysis
KW  - microRNA
KW  - sensory neuropathy
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48472
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-484728
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
VL  - 20
IS  - 4, Art. 991
SP  - 1
EP  - 19
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -