ArticleJournal of the American Society of Nephrology : JASN2015
Inhibition of intracellular clusterin attenuates cell death in nephropathic cystinosis.
Article in Journal of the American Society of Nephrology : JASN, 2015. 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, 52 citations in OpenAlex.
- Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum.International journal of molecular sciences · 2017Trial
- Liver-to-kidney apolipoprotein J trans-accumulation exacerbates diabetic renal injury by disrupting TFEB-mediated lipid homeostasis.Diabetologia · 2026Article
- Silencing Clusterin Could Attenuate the Cell Properties of HCV Core Protein-Expressing HCC Cell Line.Digestive diseases and sciences · 2026Article
- Article
- Single-Cell Atlas Reveals Tumorigenic Profiles and Immune Dynamics of Adrenal Incidentalomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Elucidating the function of clusterin in the progression of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- The pro-fibrotic role of autophagy in renal intrinsic cells: mechanisms and therapeutic potential in chronic kidney disease.Frontiers in cell and developmental biology · 2024Review
- Construction of 2DE Patterns of Plasma Proteins: Aspect of Potential Tumor Markers.International journal of molecular sciences · 2022Article
- Programmed Cell Death in Cystinosis.Cells · 2022Review
- Article
- Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys.Immunology and cell biology · 2021Article
- Plasma Osteopontin Levels is Associated with Biochemical Markers of Kidney Injury in Patients with Leptospirosis.Diagnostics (Basel, Switzerland) · 2020Article
- Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses.International journal of molecular sciences · 2020Article
- Bovine HDL and Dual Domain HDL-Mimetic Peptides Inhibit Tumor Development in Mice.Journal of cancer research and therapeutic oncology · 2020Article
- Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases.Cell death discovery · 2020Review
- Clusterin in Alzheimer's Disease: Mechanisms, Genetics, and Lessons From Other Pathologies.Frontiers in neuroscience · 2019Review
- Biomarkers associated with bronchopulmonary dysplasia/mortality in premature infants.Pediatric research · 2017Article
- Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2017Article
- Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks.Gastroenterology and hepatology from bed to bench · 2016Article
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3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nephropathic cystinosis, characterized by accumulation of cystine in the lysosomes, is caused by mutations in CTNS. The molecular and cellular mechanisms underlying proximal tubular dysfunction and progressive renal failure in nephropathic cystinosis are largely unclear, and increasing evidence supports the notion that cystine accumulation alone is not responsible for the end organ injury in cystinosis. We previously identified clusterin as potentially involved in nephropathic cystinosis. Here, we studied the expression of clusterin in renal proximal tubular epithelial cells obtained from patients with nephropathic cystinosis. The cytoprotective secretory form of clusterin, as evaluated by Western blot analysis, was low or absent in cystinosis cells compared with normal primary cells. Confocal microscopy revealed elevated levels of intracellular clusterin in cystinosis cells. Clusterin in cystinosis cells localized to the nucleus and cytoplasm and showed a filamentous and punctate aggresome-like pattern compared with diffuse cytoplasmic staining in normal cells. In kidney biopsy samples from patients with nephropathic cystinosis, clusterin protein expression was mainly limited to the proximal tubular cells. Furthermore, expression of clusterin overlapped with the expression of apoptotic proteins (apoptosis-inducing factor and cleaved caspase-3) and autophagy proteins (LC3 II and p62). Silencing of the clusterin gene resulted in a significant increase in cell viability and attenuation of apoptosis in cystinosis cells. Results of this study identify clusterin as a pivotal factor in the cell injury mechanism of nephropathic cystinosis and provide evidence linking cellular stress and injury to Fanconi syndrome and progressive renal injury in nephropathic cystinosis.
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