ArticleJournal of the American Society of Nephrology : JASN2016
Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet-Induced Kidney Disease.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 122 citations in OpenAlex.
- Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function.The Journal of clinical investigation · 2020Trial
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Review
- High-fat diet feeding induces organ-specific vascular remodeling with distinct temporal dynamics in male mice.Communications biology · 2026Article
- Article
- Fatty acids and albumin are transported by distinct mechanisms in the proximal tubule.American journal of physiology. Renal physiology · 2025Article
- Autophagic stagnation: a key mechanism in kidney disease progression linked to aging and obesity.Clinical and experimental nephrology · 2025Review
- Empagliflozin protects the kidney by reducing toxic ALB (albumin) exposure and preventing autophagic stagnation in proximal tubules.Autophagy · 2025Article
- Megalin: A Sidekick or Nemesis of the Kidney?Journal of the American Society of Nephrology : JASN · 2025Review
- Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet.bioRxiv : the preprint server for biology · 2024Article
- Megalin as a Metabolic Modulator in the Kidney and Beyond.Function (Oxford, England) · 2024Article
- The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nephron specific ATP6AP2 knockout increases urinary excretion of fatty acids and decreases renal cortical megalin expression.Scientific reports · 2024Article
- Megalin Knockout Reduces SGLT2 Expression and Sensitizes to Western Diet-induced Kidney Injury.Function (Oxford, England) · 2024Article
- Podocyte-derived soluble RARRES1 drives kidney disease progression through direct podocyte and proximal tubular injury.Kidney international · 2024Article
- Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.British journal of pharmacology · 2024Article
- Comprehensive strategy for identifying extracellular vesicle surface proteins as biomarkers for chronic kidney disease.Frontiers in physiology · 2024Review
- Transcription factor c-Maf deletion improves streptozotocin-induced diabetic nephropathy by directly regulating Sglt2 and Glut2.JCI insight · 2023Article
- Accelerated AGEing: The Impact of Advanced Glycation End Products on the Prognosis of Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.
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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.