AI Article Synopsis
- Liver fibrosis is a common chronic liver condition with significant health impact, and the role of GDF7 in this context is being explored.
- The study found that GDF7 protein levels are higher in fibrotic liver tissues, particularly in specific liver cell types, and that it promotes growth in liver organoids without activating liver stellate cells.
- The findings suggest that GDF7 could have a pro-regenerative function in liver fibrosis, indicating its potential as a therapeutic target.
Article Abstract
Background And Aim: Liver 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.
Methods: GDF7 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.
Results: GDF7 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.
Conclusions: Collectively, 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557292 | PMC |
| http://dx.doi.org/10.1186/s13287-023-03493-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!