ArticlePloS one2013
Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.Cell reports · 2026Article
- The Mechanism of KLF4-Mediated NF-κB/NLRP3 Pathway Regulating Arteriovenous Fistula Dysfunction.Acta Cardiologica Sinica · 2026Article
- Neurogranin-MYH9 interaction regulates cytoskeletal remodeling in cerebral vasculature.Fluids and barriers of the CNS · 2025Article
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- Alpha-Lipoic Acid Treatment Reduces the Levels of Advanced End Glycation Products in Type 2 Diabetes Patients with Neuropathy.Biomedicines · 2025Article
- Vascular Contractility Relies on Integrity of Progranulin Pathway: Insights Into Mitochondrial Function.Journal of the American Heart Association · 2025Article
- Progranulin, sICAM-1, and sVCAM-1 May Predict an Increased Risk for Ventricular Arrhythmias in Patients with Systemic Sclerosis.International journal of molecular sciences · 2024Article
- Review
- Multifaced roles of adipokines in endothelial cell function.Frontiers in endocrinology · 2024Review
- Adjusted vascular contractility relies on integrity of progranulin pathway: Insights into mitochondrial function.bioRxiv : the preprint server for biology · 2023Article
- The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.Cellular and molecular neurobiology · 2023Review
- Progranulin Maintains Blood Pressure and Vascular Tone Dependent on EphrinA2 and Sortilin1 Receptors and Endothelial Nitric Oxide Synthase Activation.Journal of the American Heart Association · 2023Article
- Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases.Journal of inflammation (London, England) · 2023Review
- Adipokines, adiposity, and atherosclerosis.Cellular and molecular life sciences : CMLS · 2022Review
- GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells.Diabetes & metabolism journal · 2022Article
- Determination of Serum Progranulin in Patients with Untreated Familial Hypercholesterolemia.Biomedicines · 2022Article
- Progranulin promotes osteogenic differentiation of periodontal membrane stem cells in both inflammatory and non-inflammatory conditions.The Journal of international medical research · 2021Article
- A zebrafish model of granulin deficiency reveals essential roles in myeloid cell differentiation.Blood advances · 2021Article
- Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging.Methods in molecular biology (Clifton, N.J.) · 2021Article
- In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity.Methods in molecular biology (Clifton, N.J.) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAtherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. METHOD AND
resultsSignaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis.
conclusionProgranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.
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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.