ArticlePloS one2017
Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Serum Factors in Primary Podocytopathies.Antibodies (Basel, Switzerland) · 2025Review
- Past and future in vitro and in vivo approaches toward circulating factors and biomarkers in idiopathic nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Anti-B Cell Strategy in Nephrotic Syndrome: Beyond Rituximab.Biomedicines · 2025Review
- Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders.Annual review of pathology · 2025Review
- Daratumumab combined with anti-CD20 therapy in pediatric and adult refractory idiopathic nephrotic syndrome: single-center experience.Frontiers in immunology · 2025Article
- Potential biomarkers of recurrent FSGS: a review.BMC nephrology · 2024Review
- Schizophrenia endothelial cells exhibit higher permeability and altered angiogenesis patterns in patient-derived organoids.Translational psychiatry · 2024Article
- Associations Between Mean Platelet Volume and Various Factors in Type 2 Diabetes Patients: A Single-Center Study from Poland.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors.Annals of translational medicine · 2023Article
- B cell phenotype, activity, and function in idiopathic nephrotic syndrome.Pediatric research · 2023Review
- Serum sCD40L and IL-31 in Association with Early Phase of IgA Nephropathy.Journal of clinical medicine · 2023Article
- State of the art in childhood nephrotic syndrome: concrete discoveries and unmet needs.Frontiers in immunology · 2023Review
- Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis.Frontiers in immunology · 2023Review
- New Insights into the Treatment of Glomerular Diseases: When Mechanisms Become Vivid.International journal of molecular sciences · 2022Review
- Integrated genomic, transcriptomic and metabolomic analysis reveals MDH2 mutation-induced metabolic disorder in recurrent focal segmental glomerulosclerosis.Frontiers in immunology · 2022Article
- Kidney Transplantation for Focal Segmental Glomerulosclerosis: Can We Prevent Its Recurrence? Personal Experience and Literature Review.Journal of clinical medicine · 2021Article
- The role of the immune system in idiopathic nephrotic syndrome.Molecular and cellular pediatrics · 2021Review
- CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease.Journal of clinical medicine · 2020Review
- Renal Fibrosis Is Significantly Attenuated Following Targeted Disruption ofJournal of the American Heart Association · 2020Article
- The Search for Biomarkers to Aid in Diagnosis, Differentiation, and Prognosis of Childhood Idiopathic Nephrotic Syndrome.Frontiers in pediatrics · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.
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