ArticlePloS one2019
Participation of the SMAD2/3 signalling pathway in the down regulation of megalin/LRP2 by transforming growth factor beta (TGF-ß1).
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 62 citations in OpenAlex.
- Salidroside Ameliorates Polycystic Ovary Syndrome in Mice by Regulating the AKT/NF-κB/NLRP3-HAS2 Axis.Food science & nutrition · 2026Article
- Deletion of Megalin in Kidney Tubular Epithelium Up-Regulates TGFβ1 Signaling, Aggravates Ischemia/Reperfusion Kidney Injury, and Accelerates the Progression to Chronic Kidney Disease.The American journal of pathology · 2026Article
- Plasma PZP level elevation: a potential correlate of diabetic kidney disease progression.Frontiers in medicine · 2026Article
- LRP2 Expression in Melanoma Is Associated With a Transitory Cell State, Increased T Cell Infiltration, and Is Upregulated by IFNy Signaling.Pigment cell & melanoma research · 2025Article
- Article
- High-throughput transcriptome analysis reveals a developmental increase in Acvr1c which mediates epigenetic repression of the gene encoding the pubertal brake, Makorin ring finger protein 3.NAR molecular medicine · 2025Article
- Megalin: A Sidekick or Nemesis of the Kidney?Journal of the American Society of Nephrology : JASN · 2025Review
- Vericiguat reduces atrial fibrillation recurrence by alleviating myocardial fibrosis via the TGF-β1/Smad2/3 pathway.PloS one · 2025Article
- Comprehensive Analysis of the Prognostic Marker and Immune Infiltrates of LDLR-Related Proteins Family Members in Breast Cancer.Iranian journal of pathology · 2024Article
- Low-density lipoprotein receptor promotes crosstalk between cell stemness and tumor immune microenvironment in breast cancer: a large data-based multi-omics study.Journal of translational medicine · 2023Article
- LRP2 and DOCK8 Are Potential Antigens for mRNA Vaccine Development in Immunologically 'Cold' KIRC Tumours.Vaccines · 2023Article
- Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023Review
- Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy.Frontiers in immunology · 2023Article
- Andrographolide Inhibits Corneal Fibroblast to Myofibroblast DifferentiationBiomolecules · 2022Article
- The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells.Biomedicines · 2022Article
- Functional characterization of nutraceuticals using spectral clustering: Centrality of caveolae-mediated endocytosis for management of nitric oxide and vitamin D deficiencies and atherosclerosis.Frontiers in nutrition · 2022Article
- Participation of OCRL1, and APPL1, in the expression, proteolysis, phosphorylation and endosomal trafficking of megalin: Implications for Lowe Syndrome.Frontiers in cell and developmental biology · 2022Article
- Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-βInternational journal of molecular sciences · 2021Article
- Metallothioneins and Megalin Expression Profiling in Premalignant and Malignant Oral Squamous Epithelial Lesions.Cancers · 2021Article
- The effect of aryl hydrocarbon receptor ligands on gentamicin-induced nephrotoxicity in rats.Environmental science and pollution research international · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megalin/LRP2 is a receptor that plays important roles in the physiology of several organs, such as kidney, lung, intestine, and gallbladder and also in the physiology of the nervous system. Megalin expression is reduced in diseases associated with fibrosis, including diabetic nephropathy, hepatic fibrosis and cholelithiasis, as well as in some breast and prostate cancers. One of the hallmarks of these conditions is the presence of the cytokine transforming growth factor beta (TGF-ß). Although TGF-ß has been implicated in the reduction of megalin levels, the molecular mechanism underlying this regulation is not well understood. Here, we show that treatment of two epithelial cell lines (from kidney and gallbladder) with TGF-ß1 is associated with decreased megalin mRNA and protein levels, and that these effects are reversed by inhibiting the TGF-ß1 type I receptor (TGF-ßRI). Based on in silico analyses, the two SMAD-binding elements (SBEs) in the megalin promoter are located at positions -57 and -605. Site-directed mutagenesis of the SBEs and chromatin immunoprecipitation (ChIP) experiments revealed that SMAD2/3 transcription factors interact with SBEs. Both the presence of SMAD2/3 and intact SBEs were associated with repression of the megalin promoter, in the absence as well in the presence of TGF-ß1. Also, reduced megalin expression and promoter activation triggered by high concentration of albumin are dependent on the expression of SMAD2/3. Interestingly, the histone deacetylase inhibitor Trichostatin A (TSA), which induces megalin expression, reduced the effects of TGF-ß1 on megalin mRNA levels. These data show the significance of TGF-ß and the SMAD2/3 signalling pathway in the regulation of megalin and explain the decreased megalin levels observed under conditions in which TGF-ß is upregulated, including fibrosis-associated diseases and cancer.
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