ArticleInternational journal of molecular sciences2022
Combined Therapy with a CCR2/CCR5 Antagonist and FGF21 Analogue Synergizes in Ameliorating Steatohepatitis and Fibrosis.
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 38 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Immune-inflammatory biomarkers and immune features in metabolic dysfunction-associated steatotic liver disease: a bibliometric study.Frontiers in immunology · 2026Pooled it
- AMPK-Directed Therapeutics for MASLD: Mechanistic Rationale, Activator Classes, and Clinical Translation.International journal of molecular sciences · 2026Review
- Review
- Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications.Cellular & molecular biology letters · 2026Review
- Tofogliflozin attenuates liver steatosis and fibrosis in non-diabetic non-alcoholic steatohepatitis mice.BMC gastroenterology · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Macrophages in Ulcerative Colitis: Immunomodulatory Roles, Phenotypic Switching, and Therapeutic Targeting.Journal of innate immunity · 2026Review
- The role and therapeutic prospects of intercellular communication and RNA mFrontiers in immunology · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Decoding the CHI3L1/IL-13Rα2 signaling nexus in MASH-fibrosis pathogenesis.Science advances · 2025Article
- Dual roles of T cells in metabolic dysfunction-associated steatohepatitis pathogenesis and liver fibrosis: From inflammation to therapeutic targets.Hepatology communications · 2025Review
- Therapeutic Potential of Probiotics in Metabolic Dysfunction-Associated Steatohepatitis: A Comprehensive Review.Microorganisms · 2025Review
- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
- Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome.International journal of molecular sciences · 2025Review
- Mechanism-guided drug development and treatment for liver fibrosis: a clinical perspective.Frontiers in pharmacology · 2025Review
- Prostatic Escherichia coli infection drives CCR2-dependent recruitment of fibrocytes and collagen production.Disease models & mechanisms · 2025Article
- The pivotal role of cytokines in liver disease pathogenesis and therapeutic potential.Frontiers in immunology · 2025Review
- A roadmap for clinical trials in MASH-related compensated cirrhosis.Nature reviews. Gastroenterology & hepatology · 2024Review
- FGF21-dependent alleviation of cholestasis-induced liver fibrosis by sodium butyrate.Frontiers in pharmacology · 2024Article
- NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.International journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
(1) Background: With new potential drug targets emerging, combination therapies appear attractive to treat non-alcoholic steatohepatitis (NASH) and fibrosis. Chemokine receptor CCR2/5 antagonists can improve fibrosis by reducing monocyte infiltration and altering hepatic macrophage subsets. Fibroblast growth factor 21 (FGF21) may improve NASH by modulating lipid and glucose metabolism. We compared effects of single drug to combination treatment as therapeutic strategies against NASH. (2) Methods: We analyzed serum samples and liver biopsies from 85 nonalcoholic fatty liver disease (NAFLD) patients. A CCR2/5 inhibitor (BMS-687681-02-020) and a pegylated FGF21 agonist (BMS-986171) were tested in male C57BL/6J mice subjected to dietary models of NASH and fibrosis (choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) up to 12 weeks; short- (2w) or long-term (6w) treatment). (3) Results: In NAFLD patients, chemokine CCL2 and FGF21 serum levels correlated with inflammatory serum markers, only CCL2 was significantly associated with advanced liver fibrosis. In rodent NASH, CCR2/5 inhibition significantly reduced circulating Ly6C+ monocytes and hepatic monocyte-derived macrophages, alongside reduced hepatic inflammation and fibrosis. FGF21 agonism decreased body weight, liver triglycerides and histological NASH activity. Combination treatment reflected aspects of both compounds upon short- and long-term application, thereby amplifying beneficial effects on all aspects of steatohepatitis and fibrosis. (4) Conclusions: CCR2/5 inhibition blocks hepatic infiltration of inflammatory monocytes, FGF21 agonism improves obesity-related metabolic disorders. Combined therapy ameliorates steatohepatitis and fibrosis more potently than single drug treatment in rodent NASH, corroborating the therapeutic potential of combining these two approaches in NASH patients.
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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.