ArticleJournal of neuroinflammation2019
Highly glycosylated CD147 promotes hemorrhagic transformation after rt-PA treatment in diabetes: a novel therapeutic target?
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- CD147/Basigin: From Integrative Molecular Hub to Translational Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Short-Term: Cellular Metabolism and Gene Expression During the Onset of Diabetic Kidney Disease: A Diabetes Mellitus Experimental Model.International journal of molecular sciences · 2025Article
- Novel Insights into the Mechanism and Treatment of Diabetes-Related Brain Complications: Focusing on the Blood-Brain Barrier Impairment.Aging and disease · 2025Review
- Early Use of Liraglutide for the Treatment of Acute COVID-19 Infection: An Open-Label Single-Center Phase II Safety Study with Biomarker Profiling.Infectious disease reports · 2025Article
- Extracellular Vesicles Maintain Blood-Brain Barrier Integrity by the Suppression of Caveolin-1/CD147/VEGFR2/MMP Pathway After Ischemic Stroke.International journal of nanomedicine · 2024Article
- Brain Glycogen: An Angel or a Devil for Ischemic Stroke?Neuroscience bulletin · 2023Article
- Development of a novel human CD147 knock-in NSG mouse model to test SARS-CoV-2 viral infection.Cell & bioscience · 2022Article
- Development of a Novel Human CD147 Knock-in NSG Mouse Model to Test SARS-CoV-2 Viral Infection.Research square · 2022Article
- The Role of CD147 in Pathological Cardiac Hypertrophy Is Regulated by Glycosylation.Oxidative medicine and cellular longevity · 2022Article
- Extracellular matrix metalloproteinase inducer in brain ischemia and intracerebral hemorrhage.Frontiers in immunology · 2022Review
- CD147 Levels in Blood and Adipose Tissues Correlate with Vascular Dysfunction in Obese Diabetic Adults.Journal of cardiovascular development and disease · 2021Article
- Development of a Novel Human CD147 Transgenic NSG Mouse Model to test SARS-CoV-2 Infection and Immune Responses.Research square · 2021Article
- A simple lectin-based biochip might display the potential clinical value of glycomics in patients with spontaneous intracerebral hemorrhage.Annals of translational medicine · 2021Article
- Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?Frontiers in immunology · 2021Review
- Immunohistochemical basigin expression level in thyroid cancer tissues.World journal of surgical oncology · 2020Article
- COVID-19 and Diabetes: The Importance of Controlling RAGE.Frontiers in endocrinology · 2020Article
- Impact of Diabetes in Patients Diagnosed With COVID-19.Frontiers in immunologyReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDiabetes is known to be a main risk factor of post-stroke hemorrhagic transformation following recombinant tissue plasminogen activator (rt-PA) therapy. However, the mechanism through which diabetes exacerbates hemorrhagic transformation is insufficiently understood. We aimed to verify that CD147, the extracellular matrix metalloproteinase (MMP) inducer, played a vital role in the progress.
methodsWe performed middle cerebral artery occlusion on diabetic and non-diabetic rats, with or without rt-PA treatment, and then compared the glycosylation level of CD147, caveolin-1, MMPs activities, and blood-brain barrier (BBB) permeability. In vitro, tunicamycin treatment and genetic tools were used to produce non-glycosylated and lowly glycosylated CD147. An endogenous glucagon-like peptide-1 receptor (GLP-1R) agonist was used to downregulate the glycosylation of CD147 in vivo.
resultsCompared with non-diabetic rats, diabetic rats expressed higher levels of highly glycosylated CD147 in endothelium and astrocytes following rt-PA treatment accompanied by higher activity of MMPs and BBB permeability, in the middle cerebral artery occlusion model. Caveolin-1 was also overexpressed and co-localized with CD147 in astrocytes and endothelium in diabetic rats. In vitro, advanced glycation end products increased the expression of highly glycosylated CD147 in astrocytes and endothelial cells. Downregulating the glycosylation of CD147 lowered the activity of MMPs and promoted the expression of tight junction proteins. The expression of caveolin-1 in endothelial cells and astrocytes was not inhibited by tunicamycin, which revealed that caveolin-1 was an upstream of CD147. In vivo, GLP-1R agonist downregulated the glycosylation of CD147 and further reduced the activity of MMPs and protected the BBB in diabetic rats.
conclusionCD147 is essential for diabetes-associated rt-PA-induced hemorrhagic transformation, and downregulation of CD147 glycosylation is a promising therapy for neurovascular-unit repair after rt-PA treatment of patients with diabetes.
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