ArticleGastroenterology2023
Macrophage-derived Osteopontin (SPP1) Protects From Nonalcoholic Steatohepatitis.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 123 citations in OpenAlex.
- A human single-cell atlas identifies OLR1Nature genetics · 2026Article
- The Role of the OSM/OSMRβ Axis in Chronic Liver Disease Progression and Hepatocellular Carcinoma Development: A Focus on MASLD/MASH.International journal of molecular sciences · 2026Review
- Macrophage-driven pathological ossification of the posterior longitudinal ligament: mechanistic insights and therapeutic opportunities.Bone research · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- POSTN(+) fibroblasts and SPP1(+) macrophages in scar formation: A review of mechanisms and therapeutic targets (Review).Molecular medicine reports · 2026Review
- The liver-bone axis: an emerging player in disease pathogenesis and therapeutic intervention.Science China. Life sciences · 2026Review
- Integrative Multi-Omics Analysis Elucidates the Progressive Disease Landscape and Reveals Dynamic Protein Biomarkers for MASLD Surveillance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Periportal hepatocytes secret SAA1 to recruit MoKCs and interactions through CADM1 signaling to promote MASLD.Hepatology international · 2026Article
- Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis.Nature genetics · 2026Article
- [SingleZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- JAK/STAT signaling in liver disease: a therapeutic target or a context-dependent double-edged sword?Journal of translational medicine · 2026Review
- Integrated analysis of single-cell RNA sequencing, transcriptomics, and thermal proteome profiling identifies PLCG1 as the therapeutic target of isopimpinellin in treating rheumatoid arthritis.Cellular & molecular biology letters · 2026Article
- RIPK3 Orchestrates Scar-Associated Macrophage Dysfunction to Drive Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Hepatocyte Mettl3 Deficiency Drives Primary Sclerosing Cholangitis and Liver Fibrosis via Cholangiocyte-Macrophage Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatially Resolved Multiomics Reveals Metabolic Remodeling and Autophagy Activation in Adamantinomatous Craniopharyngiomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [Characterization of liver macrophage subsets in different mouse models of metabolic associated steatohepatitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Single cell atlas decodes the molecular dynamics of scar repair after human rotator cuff tear.Bone research · 2026Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsNonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning degeneration, and fibrosis, all of which increase the risk of progression to end-stage liver disease. Osteopontin (OPN, SPP1) plays an important role in macrophage (MF) biology, but whether MF-derived OPN affects NASH progression is unknown.
methodsWe analyzed publicly available transcriptomic datasets from patients with NASH, and used mice with conditional overexpression or ablation of Spp1 in myeloid cells and liver MFs, and fed them a high-fat, fructose, and cholesterol diet mimicking the Western diet, to induce NASH.
resultsThis study demonstrated that MFs with high expression of SPP1 are enriched in patients and mice with nonalcoholic fatty liver disease (NAFLD), and show metabolic but not pro-inflammatory properties. Conditional knockin of Spp1 in myeloid cells (Spp1
conclusionMF-derived OPN protects from NASH, by upregulating OSM, which increases ARG2 through STAT3 signaling. Further, the ARG2-mediated increase in FAO reduces steatosis. Therefore, enhancing the OPN-OSM-ARG2 crosstalk between MFs and hepatocytes may be beneficial for patients with NASH.
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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.