ArticleAging cell2020
miR-195 reduces age-related blood-brain barrier leakage caused by thrombospondin-1-mediated selective autophagy.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Transport pathways across the blood-brain barrier for waste clearance and drug delivery.Fluids and barriers of the CNS · 2026Review
- Deciphering the Neuroautophagic Interactome: Molecular Circuits Linking Selective Autophagy to Neuropathological Cascades in Neurological Disorders.International journal of biological sciences · 2026Review
- Advancements in extracellular vesicle therapy for neurodegenerative diseases.Exploration of neuroprotective therapy · 2025Article
- Cellular Components of the Blood-Brain Barrier and Their Involvement in Aging-Associated Cognitive Impairment.Aging and disease · 2024Review
- Alterations of the blood-brain barrier during aging.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.International journal of clinical oncology · 2024Article
- Oxygen glucose deprivation-pretreated astrocyte-derived exosomes attenuates intracerebral hemorrhage (ICH)-induced BBB disruption through miR-27a-3p /ARHGAP25/Wnt/β-catenin axis.Fluids and barriers of the CNS · 2024Article
- Astrocyte Involvement in Blood-Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions.International journal of molecular sciences · 2023Review
- Damage mechanism and therapy progress of the blood-brain barrier after ischemic stroke.Cell & bioscience · 2023Review
- MiRNA-338-3p Inhibits Neuroinflammation in the Corpus Callosum of LCV-LPS Rats Via STAT1 Signal Pathway.Cellular and molecular neurobiology · 2023Article
- Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.Cell communication and signaling : CCS · 2023Article
- Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.Stroke · 2023Review
- Extracellular Vesicles in Mental Disorders: A State-of-art Review.International journal of biological sciences · 2023Review
- Glaesserella parasuis serotype 5 breaches the porcine respiratory epithelial barrier by inducing autophagy and blocking the cell membrane Claudin-1 replenishment.PLoS pathogens · 2022Article
- Extracellular Vesicles from miR-148a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Relieve Hepatic Fibrosis by Targeting Smad4.Molecular biotechnology · 2022Article
- Non-coding RNAs in the regulation of blood-brain barrier functions in central nervous system disorders.Fluids and barriers of the CNS · 2022Review
- MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets.International journal of molecular sciences · 2022Review
- miRNATissueAtlas2: an update to the human miRNA tissue atlas.Nucleic acids research · 2022Article
- Blood-Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive Impairment.Frontiers in cellular neuroscience · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood-brain barrier (BBB) disruption contributes to neurodegenerative diseases. Loss of tight junction (TJ) proteins in cerebral endothelial cells (ECs) is a leading cause of BBB breakdown. We recently reported that miR-195 provides vasoprotection, which urges us to explore the role of miR-195 in BBB integrity. Here, we found cerebral miR-195 levels decreased with age, and BBB leakage was significantly increased in miR-195 knockout mice. Furthermore, exosomes from miR-195-enriched astrocytes increased endothelial TJ proteins and improved BBB integrity. To decipher how miR-195 promoted BBB integrity, we first demonstrated that TJ proteins were metabolized via autophagic-lysosomal pathway and the autophagic adaptor p62 was necessary to promote TJ protein degradation in cerebral ECs. Next, proteomic analysis of exosomes revealed miR-195-suppressed thrombospondin-1 (TSP1) as a major contributor to BBB disruption. Moreover, TSP1 was demonstrated to activate selective autophagy of TJ proteins by increasing the formation of claudin-5-p62 and ZO1-p62 complexes in cerebral ECs while TSP1 impaired general autophagy. Delivering TSP1 antibody into the circulation showed dose-dependent reduction of BBB leakage by 20%-40% in 25-month-old mice. Intravenous or intracerebroventricular injection of miR-195 rescued TSP1-induced BBB leakage. Dementia patients with BBB damage had higher levels of serum TSP1 compared to those without BBB damage (p = 0.0015), while the normal subjects had the lowest TSP1 (p < 0.0001). Taken together, the study implies that TSP1-regulated selective autophagy facilitates the degradation of TJ proteins and weakens BBB integrity. An adequate level of miR-195 can suppress the autophagy-lysosome pathway via a reduction of TSP1, which may be important for maintaining BBB function.
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