ArticleThe Journal of biological chemistry2014
Mis-regulation of mammalian target of rapamycin (mTOR) complexes induced by albuminuria in proximal tubules.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Linagliptin increases the expression of LRP2 independent of Nrf2 in streptozotocin-induced diabetic mice.Journal of diabetes investigation · 2026Article
- Preoperative serum albumin levels as predictors of postoperative morbidity in pediatric congenital heart surgery: a retrospective cohort study.Annals of medicine and surgery (2012) · 2026Article
- Angiotensin receptor blocker ameliorates the development of tubulointerstitial injury and fibrosis associated with tubular proteinuria observed in subclinical diabetic kidney disease.Frontiers in pharmacology · 2026Article
- Lactobacillus johnsonii JJB3 Ameliorates Oxidative Stress-Induced Intestinal Injury and Mitochondrial Damage by Promoting BNIP3L-Mediated Mitophagy.Probiotics and antimicrobial proteins · 2026Article
- Downregulation of Akt induces proximal tubule epithelial cell apoptosis via FOXO and BIM pathway in proteinuric States.Scientific reports · 2025Article
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023Review
- Rapamycin treatment induces tubular proteinuria: role of megalin-mediated protein reabsorption.Frontiers in pharmacology · 2023Article
- Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives.International journal of molecular sciences · 2022Review
- Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin.International journal of molecular sciences · 2022Article
- Cubilin-, megalin-, and Dab2-dependent transcription revealed by CRISPR/Cas9 knockout in kidney proximal tubule cells.American journal of physiology. Renal physiology · 2022Article
- Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition.Scientific reports · 2021Article
- Effect of long term palmitate treatment on osteogenic differentiation of human mesenchymal stromal cells - Impact of albumin.Bone reports · 2020Article
- The role of lipocalin-2 in age-related macular degeneration (AMD).Cellular and molecular life sciences : CMLS · 2020Review
- IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload.Frontiers in physiology · 2020Article
- Lithium ameliorates tubule-interstitial injury through activation of the mTORC2/protein kinase B pathway.PloS one · 2019Article
- The Impairments of α-Synuclein and Mechanistic Target of Rapamycin in Rotenone-Induced SH-SY5Y Cells and Mice Model of Parkinson's Disease.Frontiers in neuroscience · 2019Article
- Article
- High glucose reduces megalin-mediated albumin endocytosis in renal proximal tubule cells through protein kinase BThe Journal of biological chemistry · 2018Article
- The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury.PloS one · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
High albumin concentrations in the proximal tubule of the kidney causes tubulointerstitial injury, but how this process occurs is not completely known. To address the signal transduction pathways mis-regulated in renal injury, we studied the modulation of mammalian target of rapamycin (mTOR) complexes by physiologic and pathophysiologic albumin concentrations in proximal tubule cells. Physiologic albumin concentrations activated the PI3K/mTORC2/PKB/mTORC1/S6 kinase (S6K) pathway, but pathophysiologically high albumin concentrations overactivated mTORC1 and inhibited mTORC2 activity. This control process involved the activation of ERK1/2, which promoted the inhibition of TSC2 and activation of S6K. Furthermore, S6K was crucial to promoting the over activation of mTORC1 and inhibition of mTORC2. Megalin expression at the luminal membrane is reduced by high concentrations of albumin. In addition, knockdown of megalin mimicked all the effects of pathophysiologic albumin concentrations, which disrupt normal signal transduction pathways and lead to an overactivation of mTORC1 and inhibition of mTORC2. These data provide new perspectives for understanding the molecular mechanisms behind the effects of albumin on the progression of renal disease.
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