Expression of MicroRNAs miR21, miR146a, and miR155 in Tuberous Sclerosis Complex Cortical Tubers and Their Regulation in Human Astrocytes and SEGA-Derived Cell Cultures

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10323841" target="_blank" >RIV/00064203:_____/16:10323841 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/16:10323841

Výsledek na webu

<a href="http://dx.doi.org/10.1002/glia.22983" target="_blank" >http://dx.doi.org/10.1002/glia.22983</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/glia.22983" target="_blank" >10.1002/glia.22983</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Expression of MicroRNAs miR21, miR146a, and miR155 in Tuberous Sclerosis Complex Cortical Tubers and Their Regulation in Human Astrocytes and SEGA-Derived Cell Cultures

Popis výsledku v původním jazyce

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-1 beta 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-1 beta and to evaluate the effects of overexpression or knockdown of miR21, miR146a, and miR155 on inflammatory signaling. IL-1 beta stimulation of cultured glial cells strongly induced intracellular miR21, miR146a, and miR155 expression, as well as miR146a extracellular release. IL-1 beta 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.

Název v anglickém jazyce

Expression of MicroRNAs miR21, miR146a, and miR155 in Tuberous Sclerosis Complex Cortical Tubers and Their Regulation in Human Astrocytes and SEGA-Derived Cell Cultures

Popis výsledku anglicky

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-1 beta 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-1 beta and to evaluate the effects of overexpression or knockdown of miR21, miR146a, and miR155 on inflammatory signaling. IL-1 beta stimulation of cultured glial cells strongly induced intracellular miR21, miR146a, and miR155 expression, as well as miR146a extracellular release. IL-1 beta 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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Glia

ISSN

0894-1491

e-ISSN

—

Svazek periodika

64

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

1066-1082

Kód UT WoS článku

000374326600014

EID výsledku v databázi Scopus

2-s2.0-84961658261