ArticleImmunity, inflammation and disease2023
Progranulin deficiency suppresses allergic asthma and enhances efferocytosis via PPAR-γ/MFG-E8 regulation in macrophages.
Article in Immunity, inflammation and disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Phagocytic aberrations in macrophages in asthma: a mechanistic systematic review integratingFrontiers in immunology · 2026Pooled it
- Effects of Progranulin Deficiency on Inflammation and Fibrosis in the Kidneys and Liver of Diabetic Mice Fed a High-Fat Diet.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Mechanistic Insights intoEndocrine, metabolic & immune disorders drug targets · 2026Article
- Efferocytosis: unifying pathogenic hub in metabolic disorders-mechanistic landscapes, targeted therapies and translational bottlenecks.Frontiers in immunology · 2026Review
- LncRNA SCARNA8 promotes atherosclerotic plaque instability by inhibiting macrophage efferocytosis.Epigenetics · 2025Article
- Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy.Molecular cancer · 2025Review
- PPAR-γ Inhibits Chronic Apical Periodontitis by Facilitating Macrophage Efferocytosis.International journal of molecular sciences · 2025Article
- Shen-Hong-Tong-Luo formula ameliorates atherosclerosis by enhancing macrophage efferocytosis through activating the PPARγ/mfge8 pathway.Frontiers in immunology · 2025Article
- Efferocytosis in Homeostasis.Advances in experimental medicine and biology · 2025Review
- PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The role of deacetylase SIRT1 in allergic diseases.Frontiers in immunology · 2024Review
- Efferocytosis and Respiratory Disease.International journal of molecular sciences · 2023Review
- Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma.International journal of molecular sciences · 2023Review
- Progranulin deficiency suppresses allergic asthma and enhances efferocytosis via PPAR-γ/MFG-E8 regulation in macrophages.Immunity, inflammation and disease · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Efferocytosis can resolve airway inflammation and enhance airway tolerance in allergic asthma. While previous work has reported that progranulin (PGRN) regulated macrophage efferocytosis, but it is unclear whether PGRN-mediated efferocytosis is associated with asthma. Here, we found that in an ovalbumin (OVA)-induced allergic asthma model, the airway inflammation was suppressed and the apoptosis in lung tissues was ameliorated in PGRN-deficient mice. In contrast, PGRN knockdown in human bronchial epithelial cells increased apoptosis in vitro. Furthermore, PGRN-deficient macrophages had significantly stronger efferocytosis ability than wild type (WT) macrophages both in vitro and in vivo. PGRN-deficient peritoneal macrophages (PMs) exhibited increased expression of genes associated with efferocytosis including milk fat globule-epidermal growth factor 8 (MFG-E8), peroxisome proliferator-activated receptor gamma (PPAR-γ) and sirtuin1 (SIRT1) and increased capacity to produce the anti-inflammatory mediator interleukin (IL)-10 during efferocytosis. GW9662, the inhibitor of PPAR-γ, abolished increased efferocytosis and MFG-E8 expression in PGRN-deficient PMs suggesting that PGRN deficiency enhanced MFG-E8-mediated efferocytosis through PPAR-γ. Correspondingly, efferocytosis genes were increased in the lungs of OVA-induced PGRN-deficient mice. GW9662 treatment reduced MFG-E8 expression but did not significantly affect airway inflammation. Our results demonstrated that PGRN deficiency enhanced efferocytosis via the PPAR-γ/MFG-E8 pathway and this may be one of the reasons PGRN deficiency results in inhibition of airway inflammation in allergic asthma.
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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 Socratic graph.