ArticleCellular and molecular gastroenterology and hepatology2023
Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis.
Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 129 citations in OpenAlex.
- Assessment of liver fibrosis and tumor burden in hepatocellular carcinoma using [European journal of nuclear medicine and molecular imaging · 2026Trial
- Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression.Med (New York, N.Y.) · 2026Review
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Article
- Molecular imaging-guided discovery of a potent natural FAPα inhibitor for liver fibrosis therapy.Nature communications · 2026Article
- A data-driven framework reconstructs the molecular continuum of human MASLD progression.Nature metabolism · 2026Article
- [Scientific reports · 2026Article
- mRNA-laden LNP-enabled in situ CAR-macrophage alleviates liver fibrosis via inhibiting activated HSCs and modulating the immune microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Fibroblast activation protein inhibitor (FAPI) PET imaging in pulmonary fibrosis: pathophysiology, clinical utility, and emerging theranostic applications.Respiratory research · 2026Review
- POSTNOncology reports · 2026Article
- CAR-T cells targeting activated hepatic stellate cells ameliorate liver fibrosis in mouse models.JHEP reports : innovation in hepatology · 2026Article
- A FAPI-based small-molecule drug conjugate alleviates rheumatoid arthritis by targeting pathogenic FAPα-expressing fibroblasts.Acta pharmacologica Sinica · 2026Article
- Proteomic profiling and pathway analyses reveal molecular signatures and immune networks in pediatric sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- ECM1 produced by hepatic stellate cells serves as a gatekeeper of liver homeostasis in hepatic fibrosis.Hepatology (Baltimore, Md.) · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- Viscoelastic hydrogel primed CAR-macrophage for pulmonary fibrosis treatment.Nature communications · 2026Article
- Combining Spatial Transcriptomics and Machine Learning Unravels Fibroblast-Related Biomarkers in Ulcerative Colitis.Inflammation · 2026Article
- Emodin: A Promising Natural Compound for Combating Fibrotic Diseases.Current medical science · 2026Review
- CAR T cell therapy for fighting IPF: perspectives on a living drug.Frontiers in immunology · 2026Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsFibroblast activation protein (FAP) is expressed on activated fibroblast. Its role in fibrosis and desmoplasia is controversial, and data on pharmacological FAP inhibition are lacking. We aimed to better define the role of FAP in liver fibrosis in vivo and in vitro.
methodsFAP expression was analyzed in mice and patients with fibrotic liver diseases of various etiologies. Fibrotic mice received a specific FAP inhibitor (FAPi) at 2 doses orally for 2 weeks during parenchymal fibrosis progression (6 weeks of carbon tetrachloride) and regression (2 weeks off carbon tetrachloride), and with biliary fibrosis (Mdr2-/-). Recombinant FAP was added to (co-)cultures of hepatic stellate cells (HSC), fibroblasts, and macrophages. Fibrosis- and inflammation-related parameters were determined biochemically, by quantitative immunohistochemistry, polymerase chain reaction, and transcriptomics.
resultsFAP+ fibroblasts/HSCs were α-smooth muscle actin (α-SMA)-negative and located at interfaces of fibrotic septa next to macrophages in murine and human livers. In parenchymal fibrosis, FAPi reduced collagen area, liver collagen content, α-SMA+ myofibroblasts, M2-type macrophages, serum alanine transaminase and aspartate aminotransferase, key fibrogenesis-related transcripts, and increased hepatocyte proliferation 10-fold. During regression, FAP was suppressed, and FAPi was ineffective. FAPi less potently inhibited biliary fibrosis. In vitro, FAP small interfering RNA reduced HSC α-SMA expression and collagen production, and FAPi suppressed their activation and proliferation. Compared with untreated macrophages, FAPi regulated macrophage profibrogenic activation and transcriptome, and their conditioned medium attenuated HSC activation, which was increased with addition of recombinant FAP.
conclusionsPharmacological FAP inhibition attenuates inflammation-predominant liver fibrosis. FAP is expressed on subsets of activated fibroblasts/HSC and promotes both macrophage and HSC profibrogenic activity in liver fibrosis.
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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.