ArticleThe American journal of pathology2005
Cyclosporine A-induced renal fibrosis: a role for epithelial-mesenchymal transition.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis 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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Immunosuppressive therapy and malignancy in organ transplant recipients: a systematic review.Drugs · 2007Pooled it
- Evaluation of molecular profiles in calcineurin inhibitor toxicity post-kidney transplant: input to chronic allograft dysfunction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Trial
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- lncRNA-mRNA Co-Expression and Regulation Analysis in Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.Non-coding RNA · 2024Article
- Tacrolimus induces fibroblast-to-myofibroblast transition via a TGF-β-dependent mechanism to contribute to renal fibrosis.American journal of physiology. Renal physiology · 2023Article
- Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-βInternational journal of molecular sciences · 2021Article
- Association Between Variants in Calcineurin Inhibitor Pharmacokinetic and Pharmacodynamic Genes and Renal Dysfunction in Adult Heart Transplant Recipients.Frontiers in genetics · 2021Article
- Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial.Journal of clinical medicine · 2020Article
- Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype.Journal of molecular cell biology · 2020Article
- Nontoxic concentration of ochratoxin A decreases the dosage of cyclosporine A to induce chronic nephropathy model via autophagy mediated by toll-like receptor 4.Cell death & disease · 2020Article
- Cyclosporine A inhibits MRTF-SRF signaling through NaFASEB bioAdvances · 2019Article
- Preclinical Study of DNA-Recognized Peptide Compound Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Progressive Renal Diseases in the Common Marmoset.Molecules (Basel, Switzerland) · 2019Article
- Calcineurin inhibitors and nephrotoxicity in children.World journal of pediatrics : WJP · 2018Review
- Possible protective effect of the algae spirulina against nephrotoxicity induced by cyclosporine A and/or gamma radiation in rats.Environmental science and pollution research international · 2018Article
- NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy.Free radical biology & medicine · 2018Article
- Epithelial to mesenchymal transition induces stem cell like phenotype in renal cell carcinoma cells.Cancer cell international · 2018Article
- Kidney Fibrosis: Origins and Interventions.Transplantation · 2017Review
- Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In Vivo.Journal of the American Society of Nephrology : JASN · 2017Article
- Klotho mitigates cyclosporine A (CsA)-induced epithelial-mesenchymal transition (EMT) and renal fibrosis in rats.International urology and nephrology · 2017Article
- Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients.American journal of translational research · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclosporine A, which has been the foremost immunosuppressive agent since the early 1980's, significantly improves the success of organ transplantation. However, common complications of cyclosporine A therapy, such as severe renal tubulointerstitial fibrosis, limit the drug's clinical use. Although the exact mechanisms driving cyclosporine A-induced tubulointerstitial fibrosis remain elusive, we hypothesized that epithelial-mesenchymal transition (EMT) may play a major role. We investigated this in vitro by treating human proximal tubular cells with cyclosporine A. Morphological changes were observed after cyclosporine A treatment, including cell elongation (with a large degree of detachment), cytoskeletal rearrangement, and junctional disruption. In addition, expression of the myofibroblast-specific marker alpha-smooth muscle actin was detected in treated cells. These observations are consistent with events described during EMT. Using Affymetrix gene microarrays, we identified 128 genes that were differentially regulated in renal tubular cells after cyclosporine A treatment, including known profibrotic factors, oncogenes, and transcriptional regulators. Cyclosporine A induced a dose-dependent increase in transforming growth factor-beta secretion from proximal tubular cells. Subsequent functional studies revealed that protein kinase C-beta isoforms play a key role in cyclosporine A-induced effects. These findings provide novel insights into cyclosporine A-induced renal fibrosis and the molecular mechanisms underlying EMT, events that may be relevant in other disease states.
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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.