ArticleJCI insight2020
The C5a/C5aR2 axis promotes renal inflammation and tissue damage.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2.Cell research · 2026Article
- Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression.International journal of molecular sciences · 2026Review
- Complement 5a receptor 2 attenuates diabetic kidney disease by promoting mitochondria-associated endoplasmic reticulum membrane formation mediated by PSS-MFN2 interaction.Cell discovery · 2026Article
- Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction.Cellular and molecular life sciences : CMLS · 2025Article
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- An anti-complement homogeneous polysaccharide fromActa pharmaceutica Sinica. B · 2025Article
- Association Between the Nutritional Inflammatory Index and Obstructive Sleep Apnea Risk: Insights from the NHANES 2015-2020 and Mendelian Randomization Analyses.Healthcare (Basel, Switzerland) · 2025Article
- Article
- A Newly Identified Protective Role of C5a Receptor 1 in Kidney Tubules against Toxin-Induced Acute Kidney Injury.The American journal of pathology · 2025Article
- Regulating Immune Responses Induced by PEGylated Messenger RNA-Lipid Nanoparticle Vaccine.Vaccines · 2024Review
- Identification of a genetic region linked to tolerance to MRSA infection using Collaborative Cross mice.PLoS genetics · 2024Article
- Cardiotrophin-1 therapy reduces disease severity in a murine model of glomerular disease.Physiological reports · 2024Article
- C5aR plus MEK inhibition durably targets the tumor milieu and reveals tumor cell phagocytosis.Life science alliance · 2024Article
- SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects.Pathogens (Basel, Switzerland) · 2024Review
- Emerging role of C5aR2: novel insights into the regulation of uterine immune cells during pregnancy.Frontiers in immunology · 2024Article
- C5aR2 Deficiency Lessens C5aR1 Distribution and Expression in Neutrophils and Macrophages.Journal of immunology research · 2024Article
- C5a/C5aR1 axis as a key driver promotes epithelial-to-mesenchymal transition in airway epithelial cells in silica nanoparticles-induced pulmonary fibrosis.International immunopharmacology · 2023Article
- Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines.International journal of molecular sciences · 2023Article
- Immune defenses in the urinary tract.Trends in immunology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
C5a is a potent inflammatory mediator that binds C5aR1 and C5aR2. Although pathogenic roles of the C5a/C5aR1 axis in inflammatory disorders are well documented, the roles for the C5a/C5aR2 axis in inflammatory disorders and underlying mechanisms remain unclear. Here, we show that the C5a/C5aR2 axis contributes to renal inflammation and tissue damage in a mouse model of acute pyelonephritis. Compared with WT littermates, C5ar2-/- mice had significantly reduced renal inflammation, tubular damage, and renal bacterial load following bladder inoculation with uropathogenic E. coli. The decrease in inflammatory responses in the kidney of C5ar2-/- mice was correlated with reduced intrarenal levels of high mobility group box-1 protein (HMGB1), NLRP3 inflammasome components, cleaved caspase-1, and IL-1β. In vitro, C5a stimulation of macrophages from C5ar1-/- mice (lacking C5aR1 but expressing C5aR2) led to significant upregulation of HMGB1 release, NLRP3/cleaved caspase-1 inflammasome activation, and IL-1β secretion. Furthermore, blockade of HMGB1 significantly reduced C5a-mediated upregulation of NLRP3/cleaved caspase-1 inflammasome activation and IL-1β secretion in the macrophages, implying a HMGB1-dependent upregulation of NLRP3/cleaved caspase-1 inflammasome activation in macrophages. Our findings demonstrate a pathogenic role for the C5a/C5aR2 axis in renal injury following renal infection and suggest that the C5a/C5aR2 axis contributes to renal inflammation and tissue damage through upregulation of HMGB1 and NLRP3/cleaved caspase-1 inflammasome.
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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.