ArticleJournal of cellular and molecular medicine2021
Complement C5 activation promotes type 2 diabetic kidney disease via activating STAT3 pathway and disrupting the gut-kidney axis.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- The cost-effectiveness of using vilobelimab with immunomodulators to treat severely ill mechanically ventilated patients with COVID-19: A subgroup analysis of the PANAMO study.American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists · 2026Trial
- Complement 5a receptor 2 attenuates diabetic kidney disease by promoting mitochondria-associated endoplasmic reticulum membrane formation mediated by PSS-MFN2 interaction.Cell discovery · 2026Article
- Causal Relationship Between Serum Zinc Levels and Diabetic Kidney Disease (DKD): A Plasma Proteomics Mediation Study.Biological trace element research · 2026Article
- The Role of Complement Component C5a in the Pathogenesis of Diabetic Kidney Disease: A New Kid on the Block?Cureus · 2026Review
- Qiling Hushen Formula Ameliorates Type 2 Diabetic Kidney Disease via Gut-Kidney Axis Restoration and TLR4/NF-κB/NLRP3 Suppression.Journal of diabetes research · 2026Article
- Gut Microbiota Dysbiosis and Metabolite Imbalance Mediate Diabetic Kidney Disease Inflammation: Mechanisms and Intervention Strategies Targeting Gut-Kidney Axis and NF-κB/NLRP3 Pathways.Journal of inflammation research · 2026Review
- Mechanism ofRenal failure · 2025Article
- Progress in the study of the role of C5a-induced tubular cell senescence in the progression of diabetic kidney disease.Annals of medicine · 2025Review
- SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational Perspectives.Journal of cardiovascular development and disease · 2025Review
- Post-ischemia and reperfusion kidney injury is mitigated in a novel complement 5 knockout rat.Physiological reports · 2025Article
- A Targeted Blockade of Terminal C5a Is Critical to Management of Sepsis and Acute Respiratory Distress Syndrome: The Mechanism of Action of Vilobelimab.International journal of molecular sciences · 2025Review
- Gut Microbiome-Derived Short-Chain Fatty Acids in Glomerular Protection and Modulation of Chronic Kidney Disease Progression.Nutrients · 2025Review
- Urinary Complement proteome strongly linked to diabetic kidney disease progression.Nature communications · 2025Article
- Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.International urology and nephrology · 2025Review
- Article
- Complement anaphylatoxins: Potential therapeutic target for diabetic kidney disease.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Complement classical and alternative pathway activation contributes to diabetic kidney disease progression: a glomerular proteomics on kidney biopsies.Scientific reports · 2025Article
- Targeting lipid metabolic reprogramming to alleviate diabetic kidney disease: molecular insights and therapeutic strategies.Frontiers in immunology · 2025Review
- Anthraquinones fromDrug design, development and therapy · 2025Review
- Gut microbiota regulates oxidative stress and inflammation: a double-edged sword in renal fibrosis.Cellular and molecular life sciences : CMLS · 2024Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Diabetic kidney disease (DKD) is a severe DM complication. While complement C5 up-regulation and gut dysbiosis are found in T2DM, their roles in DKD are unclear. Here, we investigated the effect of C5 on the gut microbiota during DKD development. Renal C5a/C5a receptor (C5aR) expression changes were measured in T2DM patients and db/db mice. Db/db mice were treated with a C5aR antagonist (C5aRA), and renal function, gut microbiota and renal genome changes were analysed. The effects of C5a and short-chain fatty acids (SCFAs) on the signal transducer and activator of transcription 3 (STAT3) pathway were examined in vitro. C5a was up-regulated in glomerular endothelial cells (GECs) of T2DM patients and db/db mice. Although glucose and lipid metabolism were unchanged, C5aR blockade alleviated renal dysfunction, ECM deposition, macrophage infiltration and proinflammatory factor expression in db/db mice. C5aRA partly reversed the declines in gut microbiota diversity and abundance and gut SCFA levels in db/db mice. C5aRA down-regulated the expression of many immune response-related genes, such as STAT3, in db/db mouse kidneys. C5aRA and SCFAs suppressed C5a-induced STAT3 activation in human renal glomerular endothelial cells (HRGECs). Based on our results, C5 hyperactivation promotes DKD by activating STAT3 in GECs and impairing the gut-kidney axis, suggesting that this hyperactivation is a potential target for the treatment of DKD.
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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.