ArticleKidney international2018
Targeted inhibition of the type 2 cannabinoid receptor is a novel approach to reduce renal fibrosis.
Article in Kidney international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- Emerging roles of cannabinoid pathways in renal injury and repair.Frontiers in pharmacology · 2026Review
- GCN-BBB: Deep Learning Blood-Brain Barrier (BBB) Permeability PharmacoAnalytics with Graph Convolutional Neural (GCN) Network.The AAPS journal · 2025Article
- Blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis.Clinical science (London, England : 1979) · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- G protein-coupled receptor-mediated renal fibrosis: a key focus on kidney disease drug development.Frontiers in pharmacology · 2025Review
- CXC chemokine receptor 7 ameliorates renal fibrosis by inhibiting β-catenin signaling and epithelial-to-mesenchymal transition in tubular epithelial cells.Renal failure · 2024Article
- Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor.The Journal of biological chemistry · 2024Article
- Virtual Screening of a Chemically Diverse "Superscaffold" Library Enables Ligand Discovery for a Key GPCR Target.ACS chemical biology · 2024Article
- The intervention of cannabinoid receptor in chronic and acute kidney disease animal models: a systematic review and meta-analysis.Diabetology & metabolic syndrome · 2024Review
- C-X-C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β-catenin-inhibited fatty acid oxidation.Journal of cellular and molecular medicine · 2024Article
- MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.Theranostics · 2024Article
- Serum granulosa cell-derived TNF-α promotes inflammation and apoptosis of renal tubular cells and PCOS-related kidney injury through NF-κB signaling.Acta pharmacologica Sinica · 2023Article
- Cannabinoid Signaling in Kidney Disease.Cells · 2023Review
- CBGA ameliorates inflammation and fibrosis in nephropathy.Scientific reports · 2023Article
- Role of Cannabinoid Type 2 Receptor Activation in Renal Fibrosis Induced by Unilateral Ureteric Obstruction in Rats.Reports of biochemistry & molecular biology · 2023Article
- A genome-wide association study identifies a possible role for cannabinoid signalling in the pathogenesis of diabetic kidney disease.Scientific reports · 2023Article
- Identification of Novel CB2 Ligands through Virtual Screening and In Vitro Evaluation.Journal of chemical information and modeling · 2023Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The cannabinoid receptor type 2 (CB2) is a G protein-coupled seven transmembrane receptor that transmits endogenous cannabinoid signaling. The role of CB2 in the pathogenesis of kidney injury and fibrosis remains poorly understood. Here we demonstrate that CB2 was induced, predominantly in kidney tubular epithelium, in various models of kidney disease induced by unilateral ureteral obstruction, adriamycin or ischemia/reperfusion injury. In vitro, forced expression of CB2 or treatment with a CB2 agonist was sufficient to trigger matrix gene expression, whereas knockdown of CB2 by siRNA abolished transforming growth factor-β1-induced signaling and fibrogenic responses in kidney tubular cells. CB2 also mediated fibroblasts and macrophage activation in vitro. Mice with genetic ablation of CB2 were protected against kidney injury after ureteral obstruction, validating a pathogenic role of CB2 in renal fibrosis in vivo. By using in silico screening and medicinal chemistry modifications, we discovered a novel compound, XL-001, that bound to CB2 with high affinity and selectivity and acted as an inverse agonist. Incubation with XL-001 inhibited in a dose-dependent fashion the fibrogenic response induced by CB2 overexpression, CB2 agonist or transforming growth factor-β1. In vivo, intraperitoneal injections of XL-001 ameliorated kidney injury, fibrosis and inflammation in both the obstruction and ischemia/reperfusion models. Delayed administration of XL-001 was also effective in ameliorating kidney fibrosis and inflammation. Thus, CB2 is a pathogenic mediator in kidney fibrosis and targeted inhibition with the novel inverse agonist XL-001 may provide a strategy in the fight against fibrotic kidney diseases.
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Registered trials
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