ArticleStem cell research & therapy2023
Growth differentiation factor 7 autocrine signaling promotes hepatic progenitor cell expansion in liver fibrosis.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 9 citations in OpenAlex.
- Cell competition driven by secreted ligands: Modeling liver metastasis of colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- High-throughput human microfluidic organoid-on-a-chip platform for modeling liver diseases and screening nanotherapeutics.Journal of nanobiotechnology · 2026Article
- Growth differentiation factor 15 mitigates lipotoxic steatosis by preserving mitochondrial morphodynamics and augmenting fatty acid oxidation in hepatocytes and liver organoids.Diabetes, obesity & metabolism · 2026Article
- Epigenetics of glaucoma in the trabecular meshwork.Clinical epigenetics · 2025Review
- Human umbilical cord mesenchymal stem cells attenuate liver fibrosis in mice and inhibit hepatic stellate cell activation by secreting soluble factors.Stem cell research & therapy · 2025Article
- TEAD4-mediated upregulation of LPAR3 augments hepatic stellate cell activation in portal hypertension.Cell biology and toxicology · 2025Article
- The metabolic shift of glutaminase 2 to glutaminase 1 promotes LGR5 + progenitor cell proliferation in liver cirrhosis.Cellular and molecular life sciences : CMLS · 2025Article
- Optimizing therapeutic outcomes: preconditioning strategies for MSC-derived extracellular vesicles.Frontiers in pharmacology · 2025Review
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimLiver fibrosis is prevalent among chronic diseases of the liver and represents a major health burden worldwide. Growth differentiation factor 7 (GDF7), a member of the TGFβ protein superfamily, has been recently investigated for its role in repair of injured organs, but its role in chronic liver diseases remains unclear. Here, we examined hepatic GDF7 expression and its association with development and progression of human liver fibrosis. Moreover, we determined the source and target cells of GDF7 in the human liver.
methodsGDF7 expression was analyzed in fibrotic and healthy human liver tissues by immunohistochemistry and qPCR. Cell-specific accumulation of GDF7 was examined by immunofluorescence through co-staining of cell type-specific markers on formalin-fixed paraffin-embedded human liver tissues. Public single cell RNA sequence databases were analyzed for cell type-specific expression of GDF7. In vitro, human liver organoids and LX-2 hepatic stellate cells (LX-2) were treated with recombinant human GDF7. Human liver organoids were co-cultured with activated LX-2 cells to induce an autocrine signaling circuit of GDF7 in liver organoids.
resultsGDF7 protein levels were elevated in fibrotic liver tissue, mainly detected in hepatocytes and cholangiocytes. In line, GDF7 mRNA was mainly detected in liver parenchymal cells. Expressions of BMPR1A and BMPR2, encoding GDF7 receptors, were readily detected in hepatocytes, cholangiocytes and stellate cells in vivo and in vitro. In vitro, recombinant GDF7 promoted liver organoid growth and enhanced expression of the progenitor cell markers (LGR5, AXIN2), but failed to activate LX-2 cells. Still, activated LX-2 cells induced GDF7 and LGR5 expression in co-cultured human liver organoids.
conclusionsCollectively, this study reveals a role of GDF7 in liver fibrosis and suggests a potential pro-regenerative function that can be utilized for amelioration of hepatic fibrosis caused by chronic liver disease.
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