ArticleMolecular endocrinology (Baltimore, Md.)2015
17β-Estradiol Ameliorates Tight Junction Disruption via Repression of MMP Transcription.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Comparison of Antioxidant Capacity and Network Pharmacology of Phloretin and Phlorizin against Neuroinflammation in Traumatic Brain Injury.Molecules (Basel, Switzerland) · 2023Pooled it
- Sexual Dimorphism in Spinal Cord Injury: From Molecular Mechanisms to Clinical Translation.Neuromolecular medicine · 2026Review
- Proteolytic Imbalance of the MMP/E-Cadherin Axis in Genitourinary Syndrome of Menopause: A Cross-Sectional Study.International journal of women's health · 2026Article
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Understanding the Blood-Brain Barrier: From Physiology to Pathology.Advances in experimental medicine and biology · 2025Review
- Exploring Sex-Related Difference in Cerebrospinal Fluid/Blood Quotient of Albumin in Older Patients Undergoing Hip Fracture Surgery: Insight From the ORTODEL and BIODEL Study.Biomarker insights · 2025Article
- Hormonal modulation, mitochondria and Alzheimer's prevention: the role of GLP-1 agonists and estrogens.Frontiers in molecular biosciences · 2025Review
- Nanoparticles in CNS Therapeutics: Pioneering Drug Delivery Advancements.Current pharmaceutical design · 2025Review
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Breaking Barriers: Unveiling Sex-Related Differences in Cerebrospinal Fluid Analysis-A Narrative Review.Biology · 2024Review
- Sex Differences in Albumin Quotient and Cerebrospinal Fluid Total Protein Content Do Not Depend on Anthropometric Factors.Journal of personalized medicine · 2024Article
- Review
- Cerebrospinal fluid/serum albumin ratio in patients with Lewy body disease: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Review
- Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders.Biomolecules · 2023Article
- Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome.Neural regeneration research · 2023Review
- Nuclear receptor ligand screening in an iPSC-derived in vitro blood-brain barrier model identifies new contributors to leptin transport.Fluids and barriers of the CNS · 2022Article
- Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases.Journal of personalized medicine · 2022Review
- The Sexual Dimorphism in Cerebrospinal Fluid Protein Content Does Not Affect Intrathecal IgG Synthesis in Multiple Sclerosis.Journal of personalized medicine · 2022Article
- Regulation of Tight Junctions by Sex Hormones in Goat Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2022Article
- Lithium therapy subdues neuroinflammation to maintain pyramidal cells arborization and rescues neurobehavioural impairments in ovariectomized rats.Molecular neurobiology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB) formed by capillary endothelial cells provides a physical wall between the central nervous system (CNS) and circulating blood with highly selective permeability. BBB/BSCB disruption by activation of matrix metalloproteinases (MMPs) has been shown to result in further neurological damage after CNS injury. Recently it has been discovered that estrogen attenuates BBB/BSCB disruption in in vitro and in vivo models. However, the molecular mechanism underlying the estrogen-mediated attenuation of BBB/BSCB disruption has not been elucidated fully. In the present study, we found that 17β-estradiol (E2) suppresses nuclear factor-κB-dependent MMP-1b, MMP-2, MMP-3, MMP-9, MMP-10, and MMP-13 gene activation in microvessel endothelial bEnd.3 cells subjected to oxygen and glucose deprivation/reperfusion injury. E2 induced the recruitment of ERα and nuclear receptor corepressor to the nuclear factor-κB binding site on the MMPs' gene promoters. Consistently, ER antagonist ICI 182.780 showed opposite effects of E2. We further found that E2 attenuates tight junction disruption through the decreased degradation of tight junction proteins in bEnd.3 cells subjected to oxygen and glucose deprivation-reperfusion injury. In addition, E2 suppressed the up-regulation of MMP expression, leading to a decreased BSCB disruption in the injured spinal cord. In conclusion, we discovered the molecular mechanism underlying the protective role of estrogenin BBB/BSCB disruption using an in vitro and in vivo model. Our study suggests that estrogens may provide a potential therapeutic intervention for preserving BBB/BSCB integrity after CNS injury.
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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.