ArticleProceedings of the National Academy of Sciences of the United States of America2000
Molecular basis for a link between complement and the vascular complications of diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 233 citations in OpenAlex.
- Plasma Glycated CD59 Predicts Early Gestational Diabetes and Large for Gestational Age Newborns.The Journal of clinical endocrinology and metabolism · 2020Trial
- Glycation of the complement regulatory protein CD59 is a novel biomarker for glucose handling in humans.The Journal of clinical endocrinology and metabolism · 2014Trial
- A specific and sensitive assay for blood levels of glycated CD59: a novel biomarker for diabetes.American journal of hematology · 2013Trial
- Glycated CD59: a novel biomarker for gestational diabetes.Endocrine reviews · 2026Review
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Targeting Complement Component 1q Ameliorates Diabetic Endothelial Inflammation Via Orphan Nuclear Receptor 4a1-Dependent Suppression of Nuclear Factor κB Signaling.Journal of the American Heart Association · 2026Article
- Urinary Complement proteome strongly linked to diabetic kidney disease progression.Nature communications · 2025Article
- The Relationship of the Plasma Glycated CD59 Level with Microvascular Complications in Diabetic Patients and Its Evaluation as a Predictive Marker.Journal of clinical medicine · 2025Article
- Chronic kidney disease enhances alternative pathway activity: a new paradigm.The Journal of clinical investigation · 2025Review
- Circulating mannose-binding lectin in diabetic patients and risk of vascular complications: a systematic review and meta-analysis.Journal of diabetes and metabolic disorders · 2024Article
- Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59.International journal of molecular sciences · 2024Article
- Pathophysiological Mechanisms of Peritoneal Fibrosis and Peritoneal Membrane Dysfunction in Peritoneal Dialysis.International journal of molecular sciences · 2024Review
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Glycated CD59 is a potential biomarker for gestational diabetes mellitus.Frontiers in endocrinology · 2024Article
- The role of complement in kidney disease.Nature reviews. Nephrology · 2023Review
- (Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins I: Localization at Plasma Membranes and Extracellular Compartments.Biomolecules · 2023Review
- Immunoregulatory Sertoli Cell Allografts Engineered to Express Human Insulin Survive Humoral-Mediated Rejection.International journal of molecular sciences · 2022Article
- The Role of Early Pregnancy Maternal pGCD59 Levels in Predicting Neonatal Hypoglycemia-Subanalysis of the DALI Study.The Journal of clinical endocrinology and metabolism · 2022Observational
- The Complement Pathway: New Insights into Immunometabolic Signaling in Diabetic Kidney Disease.Antioxidants & redox signaling · 2022Review
- The Diagnostic Accuracy of Second Trimester Plasma Glycated CD59 (pGCD59) to Identify Women with Gestational Diabetes Mellitus Based on the 75 g OGTT Using the WHO Criteria: A Prospective Study of Non-Diabetic Pregnant Women in Ireland.Journal of clinical medicine · 2022Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes.
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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.