Evidence map›Paper›PMID 31101061›Full record

ArticleJournal of neuroinflammation2019

HDAC3 inhibition prevents blood-brain barrier permeability through Nrf2 activation in type 2 diabetes male mice.

Qiuchen Zhao, Fang Zhang, Zhanyang Yu, Shuzhen Guo, Ning Liu, Yinghua Jiang, Eng H Lo, Yun Xu, Xiaoying Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 95 citations in OpenAlex.

  1. Review
  2. The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Qiuchen ZhaoDepartment of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Rd, Nanjing, 210008, Jiangsu, China.
Fang ZhangDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Zhanyang YuNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA.
Shuzhen GuoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA.
Ning LiuDepartment of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Rd, Nanjing, 210008, Jiangsu, China.
Yinghua JiangNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA.
Eng H LoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA.
Yun XuDepartment of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Rd, Nanjing, 210008, Jiangsu, China. xuyun20042001@aliyun.com.
Xiaoying WangNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA. wangxi@helix.mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USNanjing Drum Tower Hospital · CN

Funding

Jiangsu Province Key Medical Discipline ZDXKA2016020Key Research and Development Program of Jiangsu Province of China BE2016610National Key Research and Development Program of China 2016YFC1300504National Natural Science Foundation of China 81630028
6 · The paper itself

Abstract

backgroundType 2 diabetes mellitus (T2DM) is a chronic metabolic dysfunction characterized by progressive insulin resistance and hyperglycaemia. Increased blood-brain barrier (BBB) permeability is a critical neurovascular complication of T2DM that adversely affects the central nervous system homeostasis and function. Histone deacetylase 3 (HDAC3) has been reported to be elevated in T2DM animals and may promote neuroinflammation; however, its involvement in the BBB permeability of T2DM has not been investigated. In this study, we tested our hypothesis that HDAC3 expression and activity are increased in the T2DM mouse brain. Inhibition of HDAC3 may ameliorate T2DM-induced BBB permeability through Nrf2 activation.

methodsT2DM (db/db, leptin receptor-deficient), genetic non-hyperglycemic control (db/+), and wild-type male mice at the age of 16 weeks were used in this study. HDAC3 expression and activity, Nrf2 activation, and BBB permeability and junction protein expression were examined. The effects of HDAC3 activity on BBB permeability were tested using highly selective HDAC3 inhibitor RGFP966. In primary cultured human brain microvascular endothelial cells (HBMEC), hyperglycemia (25 mM glucose) plus interleukin 1 beta (20 ng/ml) (HG-IL1β) served as T2DM insult in vitro. The effects of HDAC3 on transendothelial permeability were investigated by FITC-Dextran leakage and trans-endothelial electrical resistance, and the underlying molecular mechanisms were investigated using Western blot, q-PCR, co-immunoprecipitation, and immunocytochemistry for junction protein expression, miR-200a/Keap1/Nrf2 pathway regulation.

resultsHDAC3 expression and activity were significantly increased in the hippocampus and cortex of db/db mice. Specific HDAC3 inhibition significantly ameliorated BBB permeability and junction protein downregulation in db/db mice. In cultured HBMEC, HG-IL1β insult significantly increased transendothelial permeability and reduced junction protein expression. HDAC3 inhibition significantly attenuated the transendothelial permeability and junction protein downregulation. Moreover, we demonstrated the underlying mechanism was at least in part attributed by HDAC3 inhibition-mediated miR-200a/Keap1/Nrf2 signaling pathway and downstream targeting junction protein expression in T2DM db/db mice.

conclusionsOur experimental results show that HDAC3 might be a new therapeutic target for BBB damage in T2DM.

Indexed as

AcrylamidesAnimalsBlood-Brain BarrierCell LineDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Endothelial CellsHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesHumansMaleMiceMice, Inbred C57BLMice, KnockoutNF-E2-Related Factor 2AcrylamidesHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesNfe2l2 protein, mouseNF-E2-Related Factor 2PhenylenediaminesRGFP966Blood-brain barrier (BBB)DiabetesHistone deacetylase 3 (HDAC3)HyperglycemiaInterleukin 1 beta (IL1β)NeuroinflammationNuclear factor-E2-related factor 2 (Nrf2)

Identifiers

PMID31101061
PMCPMC6525453
OpenAlexW2946867961

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.