ArticleClinical and molecular hepatology2024
Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against metabolic dysfunction-associated steatotic liver disease.
Article in Clinical and molecular hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- The association between immunoinflammatory biomarkers NLR, PLR, LMR and nonalcoholic fatty liver disease: a systematic review and meta-analysis.Clinical and experimental medicine · 2025Pooled it
- The relationship between tobacco and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis of observational studies.Frontiers in medicine · 2025Pooled it
- Widely Targeted Metabolomics Reveals Dynamic Secondary Metabolite Accumulation and Antioxidant Biomarkers Across Ripening Stages ofAntioxidants (Basel, Switzerland) · 2026Article
- Exosome-Associated Gene Network and the Role of SPP1 in Herpes Stromal Keratitis and the Therapeutic Modulation by Ursolic Acid.Investigative ophthalmology & visual science · 2026Article
- Cancer-associated fibroblasts and immune escape-related genes serve as biological markers for the prognosis of colorectal cancer.Hereditas · 2026Article
- The Role of CD4Cells · 2026Review
- Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation.Biology · 2026Review
- The SPP1-CD44 Signaling Axis Orchestrates Macrophage Metabolism to Promote Early Inflammation in Acute Kidney Injury.International journal of biological sciences · 2026Article
- Spatial transcriptomic analysis of kidney biopsies identifies activation of complement and SPP1 networks inFrontiers in nephrology · 2026Article
- Microbial exposure and host responses to infection reshape the disease trajectory of MASLD.Frontiers in cellular and infection microbiology · 2026Review
- Blocking PCSK9 suppresses hepatocellular carcinoma immune escape by decreasing FLI1-mediated SPP1 and PD-L1 expression.Journal for immunotherapy of cancer · 2025Article
- Research Progress and Prospects of Saponins in the Treatment of NAFLD: A Narrative Review.Molecules (Basel, Switzerland) · 2025Review
- Osthol ameliorates obesity-associated lipid metabolic disorders by inhibiting ADRA1D-dependent Th17 cell differentiation.Scientific reports · 2025Article
- Antihyperlipidemic Effect of Flavonoids and Saponins fromFoods (Basel, Switzerland) · 2025Article
- Negative Correlation Between Secreted Phosphoprotein 1 and the Treg/Th17 Ratio in Non-Valvular Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Article
- Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.Cellular & molecular immunology · 2025Review
- Single-cell RNA sequencing analysis of intrahepatic cholangiocarcinoma reveals SPP1 facilitates disease progression via interaction with CD4Oncology letters · 2025Article
- Identification of Schwann Cells in Human Intracranial Arteries: Potential Regulatory Role in Atherosclerotic Plaque Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumor-intrinsic ENO1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD-L1 immunotherapy in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- ncRNA-mediated ITGB1 upregulation correlates with poor prognosis and tumor-immune infiltration in gastric cancer.European journal of medical research · 2025Article
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14 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD.
methodsDrug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings.
resultsIn this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression.
conclusionUrsolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.
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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.