ArticleScientific reports2017
Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Hemorrhagic and ischemic stroke in patients with coronavirus disease 2019: incidence, risk factors, and pathogenesis - a systematic review and meta-analysis.F1000Research · 2021Pooled it
- Towards host-directed therapy: The role of matrix metalloproteinases in the immunopathogenesis of tuberculosis.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026Review
- Nitric Oxide-S-Nitrosylation and Its Role in Neuroinflammation Associated with Neuropsychiatric Conditions.International journal of molecular sciences · 2026Review
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- GlialeLife · 2026Article
- Co-expression of MARCKS and GSDMD pathway genes in tuberculous meningitis: a multi-omics analysis of blood-brain barrier disruption.Frontiers in cellular and infection microbiology · 2026Article
- Brain neurovascular unit in response to intra- and extra-central nervous system cancers: implications, mechanisms, and challenges.Cancer cell international · 2025Review
- A machine learning model and molecular clusters of epigenetic chromatin regulators in tuberculosis based on bioinformatics and clinical samples.Scientific reports · 2025Article
- Spinal Cord Injury and Ageing: The Role of Chronic Neuroinflammation.Aging and disease · 2025Review
- Group B Streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model.PLoS biology · 2025Article
- Blood-Brain Barrier Disruption in Schizophrenia: Insights, Mechanisms, and Future Directions.International journal of molecular sciences · 2025Review
- From Skin and Gut to the Brain: The Infectious Journey of the Human Commensal Fungus Malassezia and Its Neurological Consequences.Molecular neurobiology · 2025Review
- Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis.Brain communications · 2025Article
- Deciphering Tuberculous Meningitis: From Clinical Challenges to Novel Models and Pathogenic Pathways.Current topics in medicinal chemistry · 2025Review
- Matrix Metalloproteinase-9 Signaling Regulates Colon Barrier Integrity in Models of HIV Infection.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
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- Article
- TIMP-1 Protects Tight Junctions of Brain Endothelial Cells From MMP-Mediated Degradation.Pharmaceutical research · 2023Article
- The biology of SCUBE.Journal of biomedical science · 2023Review
- Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease.Biomedicines · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB.
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