ArticlePloS one2015
Tacrolimus Protects Podocytes from Injury in Lupus Nephritis Partly by Stabilizing the Cytoskeleton and Inhibiting Podocyte Apoptosis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Efficacy and safety of calcineurin inhibitor therapy in lupus nephritis: a systematic review and network meta-analysis.Frontiers in immunology · 2025Pooled it
- Disruption of podocyte cytoskeletal biomechanics by dasatinib leads to nephrotoxicity.Nature communications · 2019Pooled it
- Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients With Lupus Nephritis: A Randomized Clinical Trial.JAMA network open · 2022Trial
- Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic Syndrome.Journal of the American Society of Nephrology : JASN · 2017Trial
- Disease modification in lupus nephritis: towards a pathophysiology-based treatment paradigm.Nature reviews. Nephrology · 2026Review
- Does Voclosporin Redefine Lupus Nephritis Treatment? A Tri-Focal View of Efficacy, Safety, and Costs.Current medical science · 2026Review
- WNK1 Kinase Activity Is Required for the Functional Maintenance of Podocyte Structure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The CaPediatric nephrology (Berlin, Germany) · 2025Review
- The Spectrum of Minimal Change Disease/Focal Segmental Glomerulosclerosis: From Pathogenesis to Proteomic Biomarker Research.International journal of molecular sciences · 2025Review
- FDA-approved drugs featuring macrocycles or medium-sized rings.Archiv der Pharmazie · 2025Review
- The Role of Podocytes in Lupus Pathology.Current rheumatology reports · 2024Review
- Effect of tacrolimus with mycophenolate mofetil or cyclophosphamide on the renal response in systemic lupus erythematosus patients.BMC rheumatology · 2024Article
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- Mechanism of tacrolimus in the treatment of lupus nephritis.Frontiers in pharmacology · 2024Review
- Immune podocytes in the immune microenvironment of lupus nephritis (Review).Molecular medicine reports · 2023Review
- Review
- A network meta-analysis of randomized controlled trials comparing the effectiveness and safety of voclosporin or tacrolimus plus mycophenolate mofetil as induction treatment for lupus nephritis.Zeitschrift fur Rheumatologie · 2023Article
- Review
- Recent advances in immunotherapies for lupus nephritis.Pediatric nephrology (Berlin, Germany) · 2023Review
- [Lupus nephritis: from diagnosis to treatment].Innere Medizin (Heidelberg, Germany) · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSeveral studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function.
methodsMRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2 μm) were stained with hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-β1 for 48 h. The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy.
resultsSynaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-β1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF-β1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3.
conclusionThis study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis.
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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.