ArticleInternational journal of molecular sciences2022
TMAO Suppresses Megalin Expression and Albumin Uptake in Human Proximal Tubular Cells Via PI3K and ERK Signaling.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Gut Microbiota-Derived Metabolite and Heart Failure with Reduced Ejection Fraction (HFrEF): Elevated Trimethylamine N-Oxide (TMAO) as a Potential Biomarker.International journal of molecular sciences · 2026Article
- Antiproteinuric effect of dapagliflozin attenuates tubule-interstitial injury development in subclinical acute kidney injury animal model.Frontiers in pharmacology · 2026Article
- Advances in mechanical force-induced adaptive responses and pathological transition of renal tubular epithelial cells.Frontiers in cell and developmental biology · 2026Review
- Correlations Between Trimethylamine-N-Oxide, Megalin, Lysine and Markers of Tubular Damage in Chronic Kidney Disease.Toxins · 2025Article
- Associations of Plasma Trimethylamine N -Oxide-Related Metabolites with the Development and Progression of Albuminuria : The Multiethnic Study of Atherosclerosis.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- Trimethylamine-N-oxide (TMAO) and risk of incident cardiovascular events in the multi ethnic study of Atherosclerosis.Scientific reports · 2025Article
- The role of trimethylamine N-oxide in disease pathogenesis and the therapeutic potential of traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- Vitamin D is involved in the effects of the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys in mice with DKD.Nutrition & diabetes · 2024Article
- TMAO enhances TNF-α mediated fibrosis and release of inflammatory mediators from renal fibroblasts.Scientific reports · 2024Article
- The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison.Clinical kidney journal · 2023Review
- Trimethylamine N-Oxide (TMAO) Mediates Increased Inflammation and Colonization of Bladder Epithelial Cells during a UropathogenicPathogens (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trimethylamine-N-oxide (TMAO) is a uremic toxin, which has been associated with chronic kidney disease (CKD). Renal tubular epithelial cells play a central role in the pathophysiology of CKD. Megalin is an albumin-binding surface receptor on tubular epithelial cells, which is indispensable for urine protein reabsorption. To date, no studies have investigated the effect of TMAO on megalin expression and the functional properties of human tubular epithelial cells. The aim of this study was first to identify the functional effect of TMAO on human renal proximal tubular cells and second, to unravel the effects of TMAO on megalin-cubilin receptor expression. We found through global gene expression analysis that TMAO was associated with kidney disease. The microarray analysis also showed that megalin expression was suppressed by TMAO, which was also validated at the gene and protein level. High glucose and TMAO was shown to downregulate megalin expression and albumin uptake similarly. We also found that TMAO suppressed megalin expression via PI3K and ERK signaling. Furthermore, we showed that candesartan, dapagliflozin and enalaprilat counteracted the suppressive effect of TMAO on megalin expression. Our results may further help us unravel the role of TMAO in CKD development and to identify new therapeutic targets to counteract TMAOs effects.
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