Long Non-coding RNA H19 Promotes Leukocyte Inflammation in Ischemic Stroke by Targeting the MiR-29b/C1QTNF6 Axis

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2022 Mar 24

PMID 35322553

Authors

Guangwen Li

Xiaoqing Ma

Haiping Zhao

Junfen Fan

Tianwei Liu

Yumin Luo

Yunliang Guo

Affiliations

Soon will be listed here.

Abstract

Aims: Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non-coding RNA (lncRNA) H19-mediated regulation of C1q and tumor necrosis factor 6 (C1QTNF6) by sponging miR-29b in leukocytes during ischemic stroke.

Methods: H19 and miR-29b expression in leukocytes of patients with ischemic stroke and rats with middle cerebral artery occlusion were measured by real-time polymerase chain reaction. H19 siRNA and miR-29b antagomir were used to knock down H19 and miR-29b, respectively. We performed in vivo and in vitro experiments to determine the impact of H19 and miR-29b on C1QTNF6 expression in leukocytes after ischemic injury.

Results: H19 and C1QTNF6 upregulation, as well as miR-29b downregulation, was detected in leukocytes of patients with stroke. Moreover, miR-29b could bind C1QTNF6 mRNA and repress its expression, while H19 could sponge miR-29b to maintain C1QTNF6 expression. C1QTNF6 overexpression promoted the release of IL-1β and TNF-α in leukocytes, further exacerbated blood-brain barrier disruption, and aggravated the cerebral ischemic injury.

Conclusions: Our findings confirm that H19 promotes leukocyte inflammation by targeting the miR-29b/C1QTNF6 axis in cerebral ischemic injury.

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References

Ding R, Hase Y, Ameen-Ali K, Ndungu M, Stevenson W, Barsby J . Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease. Brain Pathol. 2020; 30(6):1087-1101. PMC: 8018063. DOI: 10.1111/bpa.12888. View

Wang J, Zhao H, Fan Z, Li G, Ma Q, Tao Z . Long Noncoding RNA H19 Promotes Neuroinflammation in Ischemic Stroke by Driving Histone Deacetylase 1-Dependent M1 Microglial Polarization. Stroke. 2017; 48(8):2211-2221. DOI: 10.1161/STROKEAHA.117.017387. View

Kim M, Lee W, Park E, Park S . C1qTNF-related protein-6 increases the expression of interleukin-10 in macrophages. Mol Cells. 2010; 30(1):59-64. DOI: 10.1007/s10059-010-0088-x. View

Longa E, Weinstein P, Carlson S, Cummins R . Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989; 20(1):84-91. DOI: 10.1161/01.str.20.1.84. View

Mendelson S, Prabhakaran S . Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review. JAMA. 2021; 325(11):1088-1098. DOI: 10.1001/jama.2020.26867. View

Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey M, Baker M . The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. J Cereb Blood Flow Metab. 2020; 40(9):1769-1777. PMC: 7430098. DOI: 10.1177/0271678X20943823. View

Huang X, Hussain B, Chang J . Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther. 2020; 27(1):36-47. PMC: 7804893. DOI: 10.1111/cns.13569. View

Wang J, Zhu M, Ye L, Chen C, She J, Song Y . MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway. Aging (Albany NY). 2020; 12(2):1141-1158. PMC: 7053628. DOI: 10.18632/aging.102672. View

Wang Y, Huang J, Ma Y, Tang G, Liu Y, Chen X . MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4. J Cereb Blood Flow Metab. 2015; 35(12):1977-84. PMC: 4671118. DOI: 10.1038/jcbfm.2015.156. View

10.

Liu W, Wang Z, Liu L, Yang Z, Liu S, Ma Z . LncRNA inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity. Proc Natl Acad Sci U S A. 2020; 117(38):23695-23706. PMC: 7519350. DOI: 10.1073/pnas.2003932117. View

11.

Wang H, Li Z, Gao J, Liao Q . Circular RNA circPTK2 regulates oxygen-glucose deprivation-activated microglia-induced hippocampal neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1β signaling. Int J Biol Macromol. 2019; 129:488-496. DOI: 10.1016/j.ijbiomac.2019.02.041. View

12.

Rodrigues S, Granger D . Blood cells and endothelial barrier function. Tissue Barriers. 2015; 3(1-2):e978720. PMC: 4372023. DOI: 10.4161/21688370.2014.978720. View

13.

Palazzo A, Koonin E . Functional Long Non-coding RNAs Evolve from Junk Transcripts. Cell. 2020; 183(5):1151-1161. DOI: 10.1016/j.cell.2020.09.047. View

14.

Cui L, Zhang Y, Chen Z, Su Y, Liu Y, Boltze J . Early neutrophil count relates to infarct size and fatal outcome after large hemispheric infarction. CNS Neurosci Ther. 2020; 26(8):829-836. PMC: 7366744. DOI: 10.1111/cns.13381. View

15.

Wang L, Cheng Q, Peng M, Lv D, Zi W, Xu G . The relationship between the platelet to leukocyte ratio and mechanical thrombectomy outcomes in acute ischemic stroke patients. Neurol Res. 2020; 42(10):890-896. DOI: 10.1080/01616412.2020.1790868. View

16.

Li S, Huang Y, Liu Y, Rocha M, Li X, Wei P . Change and predictive ability of circulating immunoregulatory lymphocytes in long-term outcomes of acute ischemic stroke. J Cereb Blood Flow Metab. 2021; 41(9):2280-2294. PMC: 8393304. DOI: 10.1177/0271678X21995694. View

17.

Xu J, Wang C, Meng F, Xu P . Long non‑coding RNA H19 inhibition ameliorates oxygen‑glucose deprivation‑induced cell apoptosis and inflammatory cytokine expression by regulating the microRNA‑29b/SIRT1/PGC‑1α axis. Mol Med Rep. 2020; 23(2). DOI: 10.3892/mmr.2020.11770. View

18.

Kirketerp-Moller N, Bayarri-Olmos R, Krogfelt K, Garred P . C1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule That Recruits Collectin-11 from the Complement System to Ligands. J Immunol. 2020; 204(6):1598-1606. DOI: 10.4049/jimmunol.1901316. View

19.

Lei X, Seldin M, Little H, Choy N, Klonisch T, Wong G . C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance. J Biol Chem. 2017; 292(36):14836-14850. PMC: 5592665. DOI: 10.1074/jbc.M116.766808. View

20.

Chen C, Huang T, Zhai X, Ma Y, Xie L, Lu B . Targeting neutrophils as a novel therapeutic strategy after stroke. J Cereb Blood Flow Metab. 2021; 41(9):2150-2161. PMC: 8393299. DOI: 10.1177/0271678X211000137. View