ArticlePloS one2015
Everolimus Stabilizes Podocyte Microtubules via Enhancing TUBB2B and DCDC2 Expression.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Renal proteomics of male offspring exposed to maternal protein restriction: molecular, epigenetic, and nephron-specific signatures of metabolic programming.Journal of physiology and biochemistry · 2026Article
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- The chromatin landscape of healthy and injured cell types in the human kidney.Nature communications · 2024Article
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes.Scientific reports · 2022Article
- A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma.Frontiers in oncology · 2022Article
- A seven-gene signature model predicts overall survival in kidney renal clear cell carcinoma.Hereditas · 2020Article
- Global proteomic analysis of insulin receptor interactors in glomerular podocytes.Wellcome open research · 2020Article
- Networks that link cytoskeletal regulators and diaphragm proteins underpin filtration function in Drosophila nephrocytes.Experimental cell research · 2018Article
- High-content screening assay-based discovery of paullones as novel podocyte-protective agents.American journal of physiology. Renal physiology · 2018Article
- Experimental Models to Study Podocyte Biology: Stock-Taking the Toolbox of Glomerular Research.Frontiers in pediatrics · 2018Review
- The Evolving Complexity of the Podocyte Cytoskeleton.Journal of the American Society of Nephrology : JASN · 2017Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte actin cytoskeleton. In contrast, a potential stabilization of microtubules by everolimus has not been studied so far.
methodsTo elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury.
resultsUpon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involved in cytoskeletal reorganization, cell adhesion, migration and extracellular matrix composition to be affected. Everolimus was capable of protecting podocytes from injury, both on transcriptional and protein level. Rescued genes included tubulin beta 2B class IIb (TUBB2B) and doublecortin domain containing 2 (DCDC2), both involved in microtubule structure formation in neuronal cells but not identified in podocytes so far. Validating gene expression data, Western-blot analysis in cultured podocytes demonstrated an increase of TUBB2B and DCDC2 protein after everolimus treatment, and immunohistochemistry in healthy control kidneys confirmed a podocyte-specific expression. Interestingly, Tubb2bbrdp/brdp mice revealed a delay in glomerular podocyte development as showed by podocyte-specific markers Wilm's tumour 1, Podocin, Nephrin and Synaptopodin.
conclusionsTaken together, our study suggests that off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development.
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