ArticleNeuropathology and applied neurobiology2020
Increased matrix metalloproteinases expression in tuberous sclerosis complex: modulation by microRNA 146a and 147b in vitro.
Article in Neuropathology and applied neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- The Mechanism Underlying the Abnormal Expression of α-Synuclein in the Cortical Lesions of Patients With FCD Type IIb and TSC.CNS neuroscience & therapeutics · 2026Article
- The Activation of the Microglial NLRP3 Inflammasome Is Involved in Tuberous Sclerosis Complex-Related Neuroinflammation.International journal of molecular sciences · 2025Article
- Epigenetic Insights into Tuberous Sclerosis Complex, Von Hippel-Lindau Syndrome, and Ataxia-Telangiectasia.Epigenomes · 2025Review
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?World journal of pediatrics : WJP · 2024Review
- LncRNA ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy.Frontiers in molecular biosciences · 2024Article
- Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2023Review
- Article
- Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers.Journal of extracellular vesicles · 2023Article
- Neurovascular Development ineNeuro · 2023Article
- A multi‑omics study of diagnostic markers and the unique inflammatory tumor micro‑environment involved in tuberous sclerosis complex‑related renal angiomyolipoma.International journal of oncology · 2022Article
- Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex.Cellular and molecular neurobiology · 2022Article
- Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors.Biomedicines · 2022Review
- Non-coding RNAs in the regulation of blood-brain barrier functions in central nervous system disorders.Fluids and barriers of the CNS · 2022Review
- Upregulation of the pathogenic transcription factor SPI1/PU.1 in tuberous sclerosis complex and focal cortical dysplasia by oxidative stress.Brain pathology (Zurich, Switzerland) · 2021Article
- The matrix metalloproteinase inhibitor IPR-179 has antiseizure and antiepileptogenic effects.The Journal of clinical investigation · 2021Article
- Dysregulation of the MMP/TIMP Proteolytic System in Subependymal Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex: Modulation of MMP by MicroRNA-320d In Vitro.Journal of neuropathology and experimental neurology · 2020Article
- Increased matrix metalloproteinases expression in tuberous sclerosis complex: modulation by microRNA 146a and 147b in vitro.Neuropathology and applied neurobiology · 2020Article
- Tuberous Sclerosis Complex as Disease Model for Investigating mTOR-Related Gliopathy During Epileptogenesis.Frontiers in neurology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimMatrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) control proteolysis within the extracellular matrix (ECM) of the brain. Dysfunction of this enzymatic system due to brain inflammation can disrupt the blood-brain barrier (BBB) and has been implicated in the pathogenesis of epilepsy. However, this has not been extensively studied in the epileptogenic human brain.
methodsWe investigated the expression and cellular localization of major MMPs (MMP2, MMP3, MMP9 and MMP14) and TIMPs (TIMP1, TIMP2, TIMP3 and TIMP4) using quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemistry in resected epileptogenic brain tissue from patients with tuberous sclerosis complex (TSC), a severe neurodevelopmental disorder characterized by intractable epilepsy and prominent neuroinflammation. Furthermore, we determined whether anti-inflammatory microRNAs, miR146a and miR147b, which can regulate gene expression at the transcriptional level, could attenuate dysregulated MMP and TIMP expression in TSC tuber-derived astroglial cultures.
resultsWe demonstrated higher mRNA and protein expression of MMPs and TIMPs in TSC tubers compared to control and perituberal brain tissue, particularly in dysmorphic neurons and giant cells, as well as in reactive astrocytes, which was associated with BBB dysfunction. More importantly, IL-1β-induced dysregulation of MMP3, TIMP2, TIMP3 and TIMP4 could be rescued by miR146a and miR147b in tuber-derived TSC cultures.
conclusionsThis study provides evidence of dysregulation of the MMP/TIMP proteolytic system in TSC, which is associated with BBB dysfunction. As dysregulated MMP and TIMP expression can be ameliorated in vitro by miR146a and miR147b, these miRNAs deserve further investigation as a novel therapeutic approach.
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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.