ArticleJCI insight2018
Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Energy metabolism in the kidney and its role in chronic kidney disease.Clinical and experimental nephrology · 2026Review
- Secreted Peptidome Profiling of Human Dental Pulp Stem Cells-Conditioned Medium During Odontogenic Differentiation.International dental journal · 2026Article
- LDLR-OPN Interaction Drives COVID-19 Myocarditis Through Monocyte Recruitment.JACC. Basic to translational science · 2026Article
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- Systems biology approach uncovers candidates for kidney-heart interorgan crosstalk after myocardial infarction.Scientific reports · 2025Article
- Hepatocyte nuclear factor 1 in renal lipid metabolism: molecular mechanisms and therapeutic potentials.Cell biology and toxicology · 2025Review
- The enzyme SMPDL3b in podocytes decouples proteinuria from chronic kidney disease progression in experimental Alport Syndrome.Kidney international · 2025Article
- Dapagliflozin, in addition to ramipril, ameliorates kidney disease progression in mice with Alport syndrome.American journal of physiology. Renal physiology · 2025Article
- Ezetimibe Enhances Lipid Droplet and Mitochondria Contact Formation, Improving Fatty Acid Transfer and Reducing Lipotoxicity in Alport Syndrome Podocytes.International journal of molecular sciences · 2024Article
- Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.Communications biology · 2024Article
- Exploration of Gene Therapy for Alport Syndrome.Biomedicines · 2024Review
- Contextualizing the Role of Osteopontin in the Inflammatory Responses of Alzheimer's Disease.Biomedicines · 2023Review
- Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease.Nature reviews. Nephrology · 2023Review
- Review
- Article
- Patient-derived podocyte spheroids reveal new insights into the etiopathogenesis of Alport syndrome.Frontiers in cell and developmental biology · 2023Article
- A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome.Genes · 2022Review
- Article
- Novel Therapies for Alport Syndrome.Frontiers in medicine · 2022Review
- Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology.Frontiers in medicine · 2022Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr-/- mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration.
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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.