ArticleCell death & disease2021
Neddylation pathway alleviates chronic pancreatitis by reducing HIF1α-CCL5-dependent macrophage infiltration.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Neddylation-dependent CUL3-KLHL12 E3 ligase drives microglial oxidative stress and neuroinflammation in traumatic brain injury by targeting GCLM for degradation.Journal of translational medicine · 2026Article
- Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity.Biomolecules · 2026Review
- IL-18 promotes pancreatic fibrosis via release of IL-4 from pancreatic stellate cells and induces macrophage M2 polarization.Scientific reports · 2026Article
- Roles of chemokines in pancreatitis: A review.World journal of gastrointestinal pathophysiology · 2025Review
- Inhibition of the neddylation E2 enzyme UBE2M in macrophages protects against E. coli-induced sepsis.The Journal of biological chemistry · 2025Article
- Metabolism and Targeted Therapy of Fibrosis in Chronic Pancreatitis: A Review.International journal of medical sciences · 2025Review
- The role of ZC3H13 in promoting M2 macrophage infiltration via m6A methylation in esophageal squamous cell carcinoma tumor progression.Frontiers in immunology · 2025Article
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- The implication of serum HLA-G in angiogenesis of multiple myeloma.Molecular medicine (Cambridge, Mass.) · 2024Article
- The Pivotal Role of Macrophages in the Pathogenesis of Pancreatic Diseases.International journal of molecular sciences · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases: Mechanisms and future perspectives.World journal of gastroenterology · 2024Review
- Targeting NEDD8 suppresses surgical stress-facilitated metastasis of colon cancer via restraining regulatory T cells.Cell death & disease · 2024Article
- New insights into SUMOylation and NEDDylation in fibrosis.Frontiers in pharmacology · 2024Review
- Cutaneous wound healing promoted by topical administration of heat-killed Lactobacillus plantarum KB131 and possible contribution of CARD9-mediated signaling.Scientific reports · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Small Tweaks, Major Changes: Post-Translational Modifications That Occur within M2 Macrophages in the Tumor Microenvironment.Cancers · 2022Review
- The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome inFrontiers in physiology · 2022Review
- Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft.Frontiers in immunology · 2022Article
- Association Between Neddylation and Immune Response.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic pancreatitis (CP) is characterized by a wide range of irreversible fibro-inflammatory diseases with largely ambiguous pathogenesis. Although neddylation pathway has been implicated in regulating immune responses, whether the dysregulation of neddylation is involved in the progression of CP and how neddylation regulates the inflammatory microenvironment of CP have not yet been reported. Here, we demonstrate that global inactivation of neddylation pathway by MLN4924 significantly exacerbates chronic pancreatitis. The increased M2 macrophage infiltration, mediated by the upregulated chemokine (C-C motif) ligand 5 (CCL5), is responsible for the enhanced pancreatitis-promoting activity of MLN4924. Both CCL5 blockade and macrophage depletion contribute to alleviating pancreatic fibrosis and inflammation in MLN4924-treated CP mice. Mechanistic investigation identifies that inactivation of Cullin-RING ligases (CRLs) stabilizes cellular levels of hypoxia-inducible factor 1α (HIF-1α), which increases CCL5 expression by promoting CCL5 transactivation. Clinically, UBE2M expression remarkably decreases in human CP tissues compared with normal specimens and the levels of CCL5 and M2 marker CD163 are negatively correlated with UBE2M intensity, suggesting that neddylation is involved in the pathogenesis of pancreatitis. Hence, our studies reveal a neddylation-associated immunopathogenesis of chronic pancreatitis and provide new ideas for the disease treatment.
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