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Long non-coding RNA and mRNA analysis of Ang II-induced neuronal dysfunction

  • Lin-Lin Shao
  • Yue-Hua Jiang
  • Ling-Yu Jiang
  • Chuan-Hua YangEmail author
  • Ying-Zi Qi
Original Article

Abstract

The sustained activation of Angiotensin II (Ang II) induces the remodelling of neurovascular units, inflammation and oxidative stress reactions in the brain. Long non-coding RNAs (lncRNAs) play a crucial regulatory role in the pathogenesis of hypertensive neuronal damage. The present study aimed to substantially extend the list of potential candidate genes involved in Ang II-related neuronal damage. This study assessed apoptosis and energy metabolism with Annexin V/PI staining and a Seahorse assay after Ang II exposure in SH-SY5Y cells. The expression of mRNA and lncRNA was investigated by transcriptome sequencing. The integrated analysis of mRNA and lncRNAs and the molecular mechanism of Ang II on neuronal injury was analysed by bioinformatics. Ang II increased the apoptosis rate and reduced the energy metabolism of SH-SY5Y cells. The data showed that 702 mRNAs and 821 lncRNAs were differentially expressed in response to Ang II exposure (244 mRNAs and 432 lncRNAs were upregulated, 458 mRNAs and 389 lncRNAs were downregulated) (fold change ≥ 1.5, P < 0.05). GO and KEGG analyses showed that both DE mRNA and DE lncRNA were enriched in the metabolism, differentiation, apoptosis and repair of nerve cells. This is the first report of the lncRNA–mRNA integrated profile of SH-SY5Y cells induced by Ang II. The novel targets revealed that the metabolism of the vitamin B group, the synthesis of unsaturated fatty acids and glycosphingolipids are involved in the Ang II-related cognitive impairment. Sphingolipid metabolism, the Hedgehog signalling pathway and vasopressin-regulated water reabsorption play important roles in nerve damage.

Keywords

Long-chain non-coding RNA MRNA Neurological dysfunction Angiotensin II 

Abbreviations

Ang II

Angiotensin II

lncRNA

Long non-coding RNA

SH-SY5Y

Human nerve cell

DMEM/F12

Dulbecco’s modified eagle medium: nutrient mixture F-12

FBS

Fetal bovine serum

OCR

Oxygen consumption rate

DE

Differential expression

FC

Fold change

GO

GeNE ontology

BP

Biological process

CC

Cellular components

MF

Molecular function

ACE2

Angiotensin converting enzyme 2

LRP2

Low-density lipoprotein receptor-related protein 2

ECEL1

Endothelin-converting enzyme-like 1

VIP

Vasoactive intestinal peptide

Notes

Acknowledgements

This study was supported by National Natural Science Foundation of China No. 81573916 and Shandong Province ‘Taishan Scholar’ Construction Project Funds No. 2018-35. We thank Yixin Yin of Shanghai Biotechnology Corporation for technical assistance and constructive suggestions.

Author Contributions

LLS, performed the experiments and drafted the manuscript. YHJ designed the study and performed the experiments. LYJ carried out methodology and data analysis. CHY designed the study, contributed to discussion and carried out important revisions of the article. YZQ contributed to data curation and software applications. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Lin-Lin Shao
    • 1
  • Yue-Hua Jiang
    • 2
  • Ling-Yu Jiang
    • 2
  • Chuan-Hua Yang
    • 2
    Email author
  • Ying-Zi Qi
    • 1
  1. 1.First Clinical Medical CollegeShandong University of Traditional Chinese MedicineJinanChina
  2. 2.Department of CardiovascularAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinanChina

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