ArticleThe American journal of pathology2004
Blockade of CCR2 ameliorates progressive fibrosis in kidney.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05997641 (A Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered DF-003 Following Single), which is not on this map. Cited by 147 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered DF-003 Following Single (Part 1) and Multiple (Part 2) Ascending Doses in Healthy Subjects
Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 335 citations in OpenAlex.
- Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review.BMC nephrology · 2017Pooled it
- Treatment outcomes and ongoing pediatric trials in steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Metabolic Reprogramming and Immunometabolic Dysregulation in Diabetic Kidney Disease: From Pathogenesis to Precision Multi-target Therapies.Research (Washington, D.C.) · 2026Review
- Macrophages and TGFB signaling regulate fibrosis in theAmerican journal of physiology. Renal physiology · 2026Article
- DMX-200 in Patients With Primary Focal Segmental Glomerulosclerosis: Results of the Phase 2 ACTION2 Trial.Kidney international reports · 2025Article
- Nonalcoholic Fatty Liver Disease Exacerbates the Advancement of Renal Fibrosis by Modulating Renal CCR2Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease.Cellular & molecular biology letters · 2025Review
- Proteomics of Urinary Extracellular Vesicles Highlight the Involvement of Vitronectin and the Fibrinolytic and TNF Pathways as Mechanisms Underlying Renal Fibrosis in Kidney Transplant Patients.Journal of extracellular biology · 2025Article
- Navigating the Complex Pathogenesis of Acute Kidney Injury: Exploring Macrophage Dynamics, Mitochondrial Dysfunction, and Ferroptosis Pathways.Advances in kidney disease and health · 2025Review
- Pharmacological antagonism of Ccr2+ cell recruitment to facilitate regenerative tendon healing.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Single-cell transcriptomic analysis reveals the association of Ccl6+Ccr2+Arg1+ macrophages with renal interstitial fibrosis in AKI.PloS one · 2025Article
- Mechanisms of prostatic inflammation-mediated male lower urinary tract symptoms.American journal of clinical and experimental urology · 2025Review
- Antagonizing CCR2 With Propagermanium Leads to Altered Distribution of Macrophage Subsets and Favorable Tissue Remodeling After Myocardial Infarction in Mice.Cardiovascular therapeutics · 2025Article
- Identification of common and specific fibrosis-related genes in three common chronic kidney diseases.Renal failure · 2024Article
- Propagermanium as a Novel Therapeutic Approach for the Treatment of Endothelial Dysfunction in Type 2 Diabetes.International journal of molecular sciences · 2024Article
- Pharmacological Antagonism of Ccr2+ Cell Recruitment to Facilitate Regenerative Tendon Healing.bioRxiv : the preprint server for biology · 2024Article
- Identification of immune-associated biomarkers of diabetes nephropathy tubulointerstitial injury based on machine learning: a bioinformatics multi-chip integrated analysis.BioData mining · 2024Article
- Review
- Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases.Inflammopharmacology · 2023Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis is a hallmark of progressive organ diseases. Monocyte chemoattractant protein (MCP)-1, also termed as macrophage chemotactic and activating factor (MCAF/CCL2) and its receptor, CCR2 are presumed to contribute to progressive fibrosis. However, the therapeutic efficacy of MCP-1/CCR2 blockade in progressive fibrosis remains to be investigated. We hypothesized that blockade of CCR2 may lead to the improvement of fibrosis. To achieve this goal, we investigated renal interstitial fibrosis induced by a unilateral ureteral obstruction in CCR2 gene-targeted mice and mice treated with propagermanium or RS-504393, CCR2 inhibitors. Cell infiltrations, most of which were F4/80-positive, were reduced in CCR2 knockout mice. In addition, dual staining revealed that CCR2-positive cells were mainly F4/80-positive macrophages. Importantly, CCR2 blockade reduced renal interstitial fibrosis relative to wild-type mice. Concomitantly, renal transcripts and protein of MCP-1, transforming growth factor-beta, and type I collagen were decreased in CCR2-null mice. Further, this CCR2-dependent loop for renal fibrosis was confirmed by treatment with CCR2 antagonists in a unilateral ureteral obstruction model. These findings suggest that the therapeutic strategy of blocking CCR2 may prove beneficial for progressive fibrosis via the decrease in infiltration and activation of macrophages in the diseased kidneys.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.