Expression of microRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA‐derived cell cultures
Abstract
Tuberous sclerosis complex (TSC) is a genetic disease presenting with multiple neurological symptoms including epilepsy, mental retardation, and autism. Abnormal activation of various inflammatory pathways has been observed in astrocytes in brain lesions associated with TSC. Increasing evidence supports the involvement of microRNAs in the regulation of astrocyte‐mediated inflammatory response. To study the role of inflammation‐related microRNAs in TSC, we employed real‐time PCR and in situ hybridization to characterize the expression of miR21, miR146a, and miR155 in TSC lesions (cortical tubers and subependymal giant cell astrocytomas, SEGAs). We observed an increased expression of miR21, miR146a, and miR155 in TSC tubers compared with control and perituberal brain tissue. Expression was localized in dysmorphic neurons, giant cells, and reactive astrocytes and positively correlated with IL‐1β expression. In addition, cultured human astrocytes and SEGA‐derived cell cultures were used to study the regulation of the expression of these miRNAs in response to the proinflammatory cytokine IL‐1β and to evaluate the effects of overexpression or knockdown of miR21, miR146a, and miR155 on inflammatory signaling. IL‐1β stimulation of cultured glial cells strongly induced intracellular miR21, miR146a, and miR155 expression, as well as miR146a extracellular release. IL‐1β signaling was differentially modulated by overexpression of miR155 or miR146a, which resulted in pro‐ or anti‐inflammatory effects, respectively. This study provides supportive evidence that inflammation‐related microRNAs play a role in TSC. In particular, miR146a and miR155 appear to be key players in the regulation of astrocyte‐mediated inflammatory response, with miR146a as most interesting anti‐inflammatory therapeutic candidate. GLIA 2016;64:1066–1082
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miR-146a-5p has immunosuppressive and anti-inflammatory functions.
“Consistent with the idea of a rescue mechanism, miR-146a-5p has well known immunosuppressive and anti-inflammatory functions [20, 35, 76].”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [76]
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Cites
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594 · see citing works
MicroRNA-146a: A Key Regulator of Astrocyte-Mediated Inflammatory Response
Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W. G. M., van Rijen, P. C., Gorter, J. A., & Aronica, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044789 · Cited by 330 · see citing works
Self-citationMicroRNA‐21 protects neurons from ischemic death
Buller, B., Liu, X., Wang, X., Zhang, R. L., Zhang, L., Hozeska‐Solgot, A., Chopp, M., & Zhang, Z. G. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07818.x · Cited by 242 · cited 2× · see citing works
“ISH showed expression in dysmorphic neurons, giant cells, and reactive astrocytes within the tuber, which is in agreement with previous studies (Bhalala et al., 2012; Buller et al., 2010; Gorter et al., 2014; Prabowo et al., 2015; Zhang et al., 2012).”
ResultMicroRNAs: New Regulators of Toll-Like Receptor Signalling Pathways
He, X., Jing, Z., & Cheng, G. (2014) · BioMed Research International · doi:10.1155/2014/945169 · Cited by 238 · see citing works
Targeting miR-21 in glioma: a small RNA with big potential
Moore, L. M., & Zhang, W. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.527334 · Cited by 51 · see citing works
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Research works printed but not linked: 3
- van Scheppingen et al.: microRNAs, Astrocytes, and TSC June 2016 1079 10981136, 2016, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/glia.22983 by Uva Universiteitsbibliotheek, Wiley Online Library on [06/11/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License · DOI
- Rao VT, Ludwin SK, Fuh SC, Sawaya R, Moore CS, Ho MK, Bedell BJ, Sarnat HB, Bar-Or A, Antel JP. MicroRNA expression patterns in human astrocytes in relation to anatomical location and age. J Neuropathol Exp Neurol, in press.
- Sethi P, Lukiw WJ. 2009. Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex. Neuro- science Letters 459:100-104.
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Prada, I., Gabrielli, M., Turola, E., Iorio, A., D’Arrigo, G., Parolisi, R., De Luca, M., Pacifici, M., Bastoni, M., Lombardi, M., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-017-1803-x · Cited by 312 · see citing works
Zimmer, T. S., Broekaart, D. W. M., Gruber, V.-E., van Vliet, E. A., Mühlebner, A., & Aronica, E. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.01028 · Cited by 48 · see citing works
Self-citationBrain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy
Brindley, E., Heiland, M., Mooney, C., Diviney, M., Mamad, O., Hill, T. D. M., Yan, Y., Venø, M. T., Reschke, C. R., Batool, A., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1230942 · Cited by 21 · see citing works
- Authors
- van Scheppingen, J., Iyer, A. M., Prabowo, A. S., Mühlebner, A., Anink, J. J., Scholl, T., Feucht, M., Jansen, F. E., Spliet, W. G., Krsek, P., Zamecnik, J., Buccoliero, A. M., Giordano, F., Genitori, L., Kotulska, K., Jozwiak, S., Jaworski, J., Liszewska, E., van Vliet, E. A., & Aronica, E.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2016-03-25
- Volume
- 64
- Issue
- 6
- Pages
- 1066-1082
- ISSN
- 0894-1491
- 1098-1136
- Cited by
- 57
- References
- 5
- Language
- en
- Update notices
- correction (2022-09-13)
- Funders
- Stichting Kinderen Kankervrij
- Austrian Science Fund (J3499)
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