ArticleJCI insight2020
C3a receptor blockade protects podocytes from injury in diabetic nephropathy.
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 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Approach to Studies on Podocyte Lesions Mediated by Hyperglycemia: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.Animal models and experimental medicine · 2023Pooled it
- ANXA1 improves mitochondrial homeostasis through uncoupling protein 1 in diabetic nephropathy.Journal of advanced research · 2026Article
- Article
- C3a/C3aR axis is involved in diabetic kidney injury by regulating podocyte mitophagy in diabetic nephropathy.International journal of molecular medicine · 2025Article
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein.Stem cell research & therapy · 2025Article
- Construction of a metabolic-immune model for predicting the risk of diabetic nephropathy and study of gut microbiota.Journal of diabetes investigation · 2025Article
- Complement anaphylatoxins: Potential therapeutic target for diabetic kidney disease.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Glucosyl Hesperidin Supplementation Prevents Tubulointerstitial Fibrosis and Immune Activation in Diabetic Nephropathy in Mice.Nutrients · 2025Article
- Complement classical and alternative pathway activation contributes to diabetic kidney disease progression: a glomerular proteomics on kidney biopsies.Scientific reports · 2025Article
- Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease.Nature communications · 2024Article
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- Urinary sC5b-9 is Better Linked to Albuminuria Than to Intrarenal Inflammation in Common Kidney Disease.Kidney international reports · 2024Article
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation.Acta pharmaceutica Sinica. B · 2024Article
- Landscape of infiltrating immune cells and related genes in diabetic kidney disease.Clinical and experimental nephrology · 2024Article
- Complement Cascade Proteins Correlate with Fibrosis and Inflammation in Early-Stage Type 1 Diabetic Kidney Disease in the Ins2Akita Mouse Model.International journal of molecular sciences · 2024Article
- The role of innate immunity in diabetic nephropathy and their therapeutic consequences.Journal of pharmaceutical analysis · 2024Review
- Shared signaling pathways and comprehensive therapeutic approaches among diabetes complications.Frontiers in medicine · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal activation of the complement system has been described in patients with diabetic nephropathy (DN), although its pathological relevance is still ill-defined. Here, we studied whether glomerular C3a, generated by uncontrolled complement activation, promotes podocyte damage, leading to proteinuria and renal injury in mice with type 2 diabetes. BTBR ob/ob mice exhibited podocyte loss, albuminuria, and glomerular injury accompanied by C3 deposits and increased C3a and C3a receptor (C3aR) levels. Decreased glomerular nephrin and α-actinin4 expression, coupled with integrin-linked kinase induction, were also observed. Treatment of DN mice with a C3aR antagonist enhanced podocyte density and preserved their phenotype, limiting proteinuria and glomerular injury. Mechanistically, ultrastructural and functional mitochondrial alterations, accompanied by downregulation of antioxidant superoxide dismutase 2 (SOD2) and increased protein oxidation, occurred in podocytes and were normalized by C3aR blockade. In cultured podocytes, C3a induced cAMP-dependent mitochondrial fragmentation. Alterations of mitochondrial membrane potential, SOD2 expression, and energetic metabolism were also found in response to C3a. Notably, C3a-induced podocyte motility was inhibited by SS-31, a peptide with mitochondrial protective effects. These data indicate that C3a blockade represents a potentially novel therapeutic strategy in DN for preserving podocyte integrity through the maintenance of mitochondrial functions.
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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.