ArticleActa pharmacologica Sinica2022
Intrarenal 1-methoxypyrene, an aryl hydrocarbon receptor agonist, mediates progressive tubulointerstitial fibrosis in mice.
Article in Acta pharmacologica Sinica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 3 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 66 citations in OpenAlex.
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- Saliva urea nitrogen for detection of kidney disease in adults: A meta-analysis of diagnostic test accuracy.PloS one · 2025Pooled it
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- Renal Tubular Epithelial Cells Senescence Induced by 1-Aminopyrene Activates Fibroblast via BRD4 Driven Senescence-Associated Secretory Phenotype Signaling.Journal of biochemical and molecular toxicology · 2026Article
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- Autophagy and Mitophagy in Hypertensive Chronic Kidney Disease: Evidence Grading, Cell-Type Divergence, and a Working Lysosomal Hypothesis.Life (Basel, Switzerland) · 2026Review
- Grain proteins ameliorate glucose metabolism disorders by activating intestinal AhR and the hepatic NLK/FOXO1 pathway via gut microbiota-derived indole metabolites.Journal of advanced research · 2026Article
- Huang'e Capsule Alleviates Experimental Autoimmune Prostatitis in Rats Through Regulation of Linoleic Acid and Arachidonic Acid Metabolism by Metabolomics.Biomedical chromatography : BMC · 2026Article
- Indoxyl Sulfate Promotes Vascular Calcification in Association with Oxidative Stress and Activation of ERK and Wnt/β-Catenin Signaling Pathways.International journal of molecular sciences · 2026Article
- Abatacept-Loaded Podocyte-Derived Exosomes Alleviate Membranous Nephropathy via AhR-Regulated NF-κB/Nrf2 Signaling under Oxidative Stress and Inflammation.Applied biochemistry and biotechnology · 2026Article
- Trans fatty acids alter renal health in TGFβ3 mice with fibrosis revealed by metabolomics and lipidomics.iScience · 2026Article
- Ginsenoside RgJournal of natural medicines · 2026Article
- Unveiling the therapeutic potential of gut microbiota metabolites for the treatment of renal fibrosis based on network pharmacology study.Bioresources and bioprocessing · 2026Article
- Gastrodin as a nephroprotective agent: Molecular docking-based modulation of oxidative stress, fibrosis, and inflammation.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Ureic clearance granule ameliorates chronic kidney disease by reshaping microbial dysbiosis via modulating bile acid metabolism.Chinese medicine · 2026Article
- Aryl hydrocarbon receptor in the kidney regulates metabolic cross-talk with the liver and gut microbiome.Scientific reports · 2026Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have shown that endogenous metabolites act via aryl hydrocarbon receptor (AhR) signalling pathway in tubulointerstitial fibrosis (TIF) pathogenesis. However, the mechanisms underlying endogenous metabolite-mediated AhR activation are poorly characterised. In this study, we conducted untargeted metabolomics analysis to identify the significantly altered intrarenal metabolites in a mouse model of unilateral ureteral obstruction (UUO). We found that the levels of the metabolite 1-methoxypyrene (MP) and the mRNA expression of AhR and its target genes CYP1A1, CYP1A2, CYP1B1 and COX-2 were progressively increased in the obstructed kidney at Weeks 1, 2 and 3. Furthermore, these changes were positively correlated with progressive TIF in UUO mice. In NRK-52E, RAW 264.7 and NRK-49F cells, MP dose-dependently upregulated the mRNA expression of AhR and its four target genes and the protein expression of nuclear AhR, accompanied by the upregulated protein expression of collagen I, α-SMA and fibronectin, as well as downregulated E-cadherin expression. Consistently, oral administration of MP in mice progressively enhanced AhR activity and upregulated profibrotic protein expression in the kidneys; these effects were partially inhibited by AhR knockdown in MP-treated mice and cell lines. In addition, we screened and identified erythro-guaiacylglycerol-β-ferulic acid ether (GFA), which was isolated from Semen plantaginis, as a new AhR antagonist. GFA significantly attenuated TIF in MP-treated NRK-52E cells and mice by partially antagonising AhR activity. Our results suggest that MP activates AhR signalling, thus mediating TIF through epithelial-mesenchymal transition and macrophage-myofibroblast transition. MP is a crucial metabolite that contributes to TIF via AhR signalling pathway.
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