Dataset Information

High-throughput sequencing analysis of lncRNAs in hippocampus tissues with hypoxic-ischemic brain damage.

ABSTRACT: LncRNAs abundantly expressed in the brain have vital and wide-ranging functions in different biological processes. However, little is currently known regarding the influence of lncRNAs in developing brains after hypoxic-ischemic brain damage (HIBD). In this study, to investigate the lncRNAs expression signatures and the co-expression network of lncRNAs and mRNAs in the brain after HIBD, we established a neonatal rat HIBD model and detected the expression profiles of lncRNAs in the HIBD brain and a sham control using high-throughput sequencing. Further, highly differentially expressed lncRNAs were selected and validated by qRT-PCR. Finally, the biological functions of the selected lncRNAs were investigated by over-expressing or silencing the target genes through lentivirus transfection in hippocampal neuron cells. Our results revealed that the expression profile of lncRNAs was dramatically different between the HIBD brains and the sham control, showing as the aberrant expression of 617 lncRNA transcripts and 441 mRNA transcripts at 24 hours after HIBD. GO and KEGG analyses indicated that the differentially expressed mRNAs were mostly involved in the apoptosis signaling pathway. After validating the expression of 8 randomly selected lncRNA transcripts by qRT-PCR, we found that the TNFRSF17 gene (ID: ENSRNOG00000021987) was down-regulated in HI brains. After stable over-expression and silencing of TNFRSF17, the apoptosis rate of hippocampal neuron cells exhibited obvious changes under hypoxia or normaxia. The over-expression of TNFRSF17 could significantly up-regulate Bcl-2 but down-regulate Bax, caspase-3, and caspase-9 at the mRNA and protein levels, while the silencing of TNFRSF17 led to just the opposite phenomenon. Notably, the regulation effects of TNFRSF17 on apoptotic related genes and proteins under hypoxia were more obvious than those under normaxia. Moreover, the over-expression of TNFRSF17 reduced the apoptotic rate, but the loss of TNFRSF17 led to a high rate of apoptosis under hypoxia. Taken together, the silencing of TNFRSF17 exacerbated, while over-expression attenuated, neuron apoptosis induced by HI injury, suggesting that TNFRSF17 may be a target for the prognosis, diagnosis, and treatment of HIBD.

SUBMITTER: Zhao RB

PROVIDER: S-EPMC6963025 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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High-throughput sequencing analysis of lncRNAs in hippocampus tissues with hypoxic-ischemic brain damage.

Zhao Rui-Bin RB Zhu Li-Hua LH Li Hui-Juan HJ Fan Zhong-Min ZM Xia Zheng-Kun ZK

International journal of clinical and experimental pathology 20181101 11

LncRNAs abundantly expressed in the brain have vital and wide-ranging functions in different biological processes. However, little is currently known regarding the influence of lncRNAs in developing brains after hypoxic-ischemic brain damage (HIBD). In this study, to investigate the lncRNAs expression signatures and the co-expression network of lncRNAs and mRNAs in the brain after HIBD, we established a <i>neonatal rat HIBD model</i> and detected the expression profiles of lncRNAs in the HIBD br ...[more]

PMID: 31949607

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Project description:BackgroundAngiogenesis is an endogenous repair mechanism following hypoxic-ischemic brain damage (HIBD). Interestingly, recent studies have shown that angiogenesis can be regulated by telomerase reverse transcriptase (TERT), a critical component of telomerase. As telomerase reverse transcriptase can promote angiogenesis after stroke, we hypothesized that it could also promote angiogenesis after HIBD. To test this hypothesis, we developed in vivo and in vitro HIBD models in neonatal rats.MethodsTERT was overexpressed by lentivirus and adenovirus infection, and levels were measured using quantitative real-time polymerase chain reaction. We used a cell counting kit to quantify the proliferation rate of brain microvascular endothelial cells (BMECs), and immunofluorescence staining to measure CD34 expression levels. A microvessel formation assay was used to evaluate angiogenesis. Blood-brain barrier (BBB) integrity was assessed using immunohistochemical staining for ZO-1 and Evans Blue staining. Lastly, the expression level of Notch-1 was measured by western blotting.ResultsOverexpression of TERT promoted the proliferation of BMECs after hypoxic-ischemic damage in vitro. TERT overexpression increased the formation of microvessels in the neonatal brain after HIBD both in vivo and in vitro. Overexpression of TERT improved BBB integrity in the brains of neonatal rats after HIBD. In addition, the expression level of Notch-1 was increased in BMECs following oxygen glucose deprivation, and overexpression of TERT further increased Notch-1 expression levels in BMECs following oxygen glucose deprivation.DiscussionOur results reveal that telomerase reverse transcriptase promotes angiogenesis and maintains the integrity of the blood-brain barrier after neonatal hypoxic-ischemic brain damage. Furthermore, the Notch-1 signaling pathway appears to contribute to the angiogenic function of telomerase reverse transcriptase. This protective effect of telomerase reverse transcriptase opens new horizons for future investigations aimed at uncovering the full potential of telomerase reverse transcriptase as a promising new target for the treatment of hypoxic-ischemic encephalopathy.

Dataset Information

High-throughput sequencing analysis of lncRNAs in hippocampus tissues with hypoxic-ischemic brain damage.

Publications

High-throughput sequencing analysis of lncRNAs in hippocampus tissues with hypoxic-ischemic brain damage.

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