ArticlePharmaceutical research2023
TIMP-1 Protects Tight Junctions of Brain Endothelial Cells From MMP-Mediated Degradation.
Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unit.bioRxiv : the preprint server for biology · 2026Article
- Microcystin-LR Impairs Endometrial Receptivity during the Peri-Implantation Window via Disruption of STAT3/HIF-1α Signaling.Environment & health (Washington, D.C.) · 2026Article
- Research on the Molecular Mechanism of Ginsenoside Ro in Neuronal Damage Following Subarachnoid Hemorrhage.ACS omega · 2026Article
- Correlations of thrombus MMP-9 level with clinical characteristics and inflammatory markers in acute ischemic stroke.BMC neurology · 2026Article
- Ang II-mediated effects on BBB integrity in psychiatric and neurological disorders.Progress in neuro-psychopharmacology & biological psychiatry · 2026Review
- Gestational hypoxia increases brain-blood barrier permeability in the neonatal cerebral cortex of Guinea pigs.Pediatric research · 2026Article
- The loss of glycoprotein nonmetastatic melanoma protein B (GPNMB) alters endothelial cell permeability, metabolism, and survival during infectious challenge.Clinical science (London, England : 1979) · 2026Article
- Evaluating the effect of minimal TIMP variants on protecting and transport across the rat brain microvascular cells (RBMEC).Scientific reports · 2025Article
- The protective role of nuclear Heme oxygenase-1 in blood-spinal cord barrier after hypoxia in vitro.Scientific reports · 2025Article
- Synergistic Neuroprotection of Artesunate and Tetramethylpyrazine in Ischemic Stroke, Mechanisms of Blood-Brain Barrier Preservation.International journal of molecular sciences · 2025Article
- Exosomal MicroRNA: an Effective Strategy for the Treatment of Intracerebral Hemorrhage.Molecular neurobiology · 2025Review
- TIMP1 secretion induced bymSphere · 2025Article
- Effects of Different Doses of Glucosamine Hydrochloride on Cartilage Tissue and Levels of Joint Injury Markers in Knee Osteoarthritis.Journal of cellular and molecular medicine · 2025Article
- Matrix Dynamics and Microbiome Crosstalk: Matrix Metalloproteinases as Key Players in Disease and Therapy.International journal of molecular sciences · 2025Review
- Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells.Oncotarget · 2025Article
- The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.Journal of clinical medicine · 2025Review
- Mechanisms and potential therapeutic molecular targets in blood-brain barrier disruption following subarachnoid hemorrhage: a review of early brain injury.Frontiers in neurology · 2025Review
- Targeting the blood-brain barrier with phytochemicals to attenuate vascular cognitive impairment: mechanisms and therapeutic potential across etiologies.Frontiers in nutrition · 2025Review
- Determining key residues of engineered scFv antibody variants with improved MMP-9 binding using deep sequencing and machine learning.Computational and structural biotechnology journal · 2024Article
- The Preventive Effect of Ulinastatin on Blood-Brain Barrier Dysfunction in Rats with Postoperative Cognitive Dysfunction After General Anaesthesia with Isoflurane.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe blood-brain barrier (BBB) plays a critical role in central nervous system homeostasis, and the integrity of BBB is disrupted in many neurodegenerative diseases. Matrix metalloproteinases (MMPs) degrade the tight junctions (TJs) of endothelial cells and basement membrane components essential to BBB integrity, which leads to increased BBB permeability and allows inflammatory cells and neurotoxic substances to enter the brain. Tissue inhibitors of metalloproteinases (TIMPs), endogenous inhibitors of MMPs, regulate MMP activity, thereby maintaining BBB integrity.
methodsThe disruptive impacts of MMP-3 and MMP-9 on BBB and protective effect of TIMP-1 were investigated in a simplified in vitro model of the BBB, which was generated using rat brain microvascular endothelial cells (RBMEC). The main features of BBB formation, including permeability and the trans-endothelial electrical resistance (TEER), were monitored over time after the addition of MMP-3 and MMP-9 and their complexes with TIMP-1 inhibitor.
resultsOur results indicated that MMP-3 and MMP-9 caused a dose-dependent disruption of the BBB, with 1.5 µM MMPs resulting in an over threefold increase in permeability, while TIMP-1 inhibition protected the integrity of the BBB model and recovered TEER and permeability of RBMECs. The disruption and recovery of tight junction proteins of RBMECs after MMP and TIMP treatment were also detected using fluorescent microscopy.
conclusionMMP-9 and MMP-3 disrupt the BBB by degrading tight junctions in endothelial cells, and TIMP-1 could inhibit the disruptive effect of MMP-3 and MMP-9 by showing potential as therapeutic protein against MMP-related diseases where BBB disruption plays a role.
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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.