ArticleCellular and molecular neurobiology2019
MALAT1 Up-Regulator Polydatin Protects Brain Microvascular Integrity and Ameliorates Stroke Through C/EBPβ/MALAT1/CREB/PGC-1α/PPARγ Pathway.
Article in Cellular and molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Systems-level analysis uncovers eight hub genes and a resveratrol-based therapeutic strategy for ischemic stroke.Frontiers in pharmacology · 2026Article
- Investigating the Mechanisms of Mitochondrial Dysfunction in Ischemic Stroke and Predicting Therapeutics Through Machine Learning and Integrated Bioinformatics.Current medicinal chemistry · 2026Article
- Electroacupuncture Serum Alleviates Ogd/R-Induced Astrocyte Damage by Regulating the AQP4 Via m6A Methylation of lncRNA MALAT1.Neurochemical research · 2025Article
- Long Non-coding RNA Involved in the Pathophysiology of Atrial Fibrillation.Cardiovascular drugs and therapy · 2025Review
- Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood-Brain Barrier in Diseases.Nutrients · 2025Review
- Targeting microglia polarization with Chinese herb-derived natural compounds for neuroprotection in ischemic stroke.Frontiers in cell and developmental biology · 2025Review
- Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling.Open life sciences · 2025Article
- LncRNA MALAT1 and Ischemic Stroke: Pathogenesis and Opportunities.Molecular neurobiology · 2024Review
- Dexmedetomidine Alleviates Brain Ischemia/Reperfusion Injury by Regulating Metastasis-associated Lung Adenocarcinoma Transcript 1/MicroRNA-140-5p/ Nuclear Factor Erythroid-derived 2-like 2 Axis.Protein and peptide letters · 2024Article
- Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy.Current medicinal chemistry · 2024Review
- Targeting Non-Coding RNA for CNS Injuries: Regulation of Blood-Brain Barrier Functions.Neurochemical research · 2023Review
- LncRNA-MALAT1: A Key Participant in the Occurrence and Development of Cancer.Molecules (Basel, Switzerland) · 2023Review
- Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.Molecules (Basel, Switzerland) · 2022Review
- Andrographolide in atherosclerosis: integrating network pharmacology and in vitro pharmacological evaluation.Bioscience reports · 2022Article
- Infarct-preconditioning exosomes of umbilical cord mesenchymal stem cells promoted vascular remodeling and neurological recovery after stroke in rats.Stem cell research & therapy · 2022Article
- An update on the functional roles of long non‑coding RNAs in ischemic injury (Review).International journal of molecular medicine · 2022Review
- Polyphenols for the Treatment of Ischemic Stroke: New Applications and Insights.Molecules (Basel, Switzerland) · 2022Review
- Non-coding RNAs in the regulation of blood-brain barrier functions in central nervous system disorders.Fluids and barriers of the CNS · 2022Review
- Stroke Genomics: Current Knowledge, Clinical Applications and Future Possibilities.Brain sciences · 2022Review
- A narrative review of long noncoding RNA: insight into neural ischemia/reperfusion mediated by two pathophysiological processes of injury and repair.Annals of translational medicine · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA contributing to protect the blood-brain barrier (BBB) after stroke. We searched for small molecules that may up-regulate MALAT1 and focused on polydatin (PD), a natural product, as a possible candidate. PD enhanced MALAT1 gene expression in rat brain microvascular endothelial cells, reducing cell toxicity and apoptosis after oxygen and glucose deprivation (OGD). These effects correlated with reduction of inflammatory factors and enhancement of expression of BBB markers. We found opposite changes after MALAT1 silencing. We determined that C/EBPβ is a key transcription factor for PD-mediated MALAT1 expression. PPARγ activity is involved in MALAT1 protective effects through its coactivator PGC-1α and the transcription factor CREB. This suggests that PD activates the MALAT1/CREB/PGC-1α/PPARγ signaling pathway to protect endothelial cells against ischemia. PD administration to rats subjected to brain ischemia by transient middle cerebral artery occlusion (tMCAO) reduced cerebral infarct volume and brain inflammation, protected cerebrovascular endothelial cells and BBB integrity. These effects correlated with increased expression of MALAT1, C/EBPβ, and PGC-1α. Our results strongly suggest that the beneficial effects of PD involve the C/EBPβ/MALAT1/CREB/PGC-1α/PPARγ pathway, which may provide a novel therapeutic strategy for brain ischemic stroke.
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Registered trials
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.