ArticleDigestive diseases and sciences2014
R-spondin2 activates hepatic stellate cells and promotes liver fibrosis.
Article in Digestive diseases and sciences, 2014. 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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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- The biological functions and related signaling pathways of SPON2.Frontiers in oncology · 2023Review
- The role of roof plate-specific spondins in liver homeostasis and disease.Liver research (Beijing, China) · 2022Review
- Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options: An Update.Journal of clinical and translational hepatology · 2021Review
- Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model.Gut microbes · 2020Article
- Insulin-Like Growth Factor Binding Protein-Related Protein 1 Activates Primary Hepatic Stellate Cells via Autophagy Regulated by the PI3K/Akt/mTOR Signaling Pathway.Digestive diseases and sciences · 2020Article
- Targeting the Wnt signaling pathway through R-spondin 3 identifies an anti-fibrosis treatment strategy for multiple organs.PloS one · 2020Article
- Elimination of Wnt Secretion From Stellate Cells Is Dispensable for Zonation and Development of Liver Fibrosis Following Hepatobiliary Injury.Gene expression · 2019Article
- R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma.Oncology letters · 2017Article
- Immunohistochemical Analysis of the Stem Cell Marker LGR5 in Pediatric Liver Disease.Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyArticle
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe development of liver fibrosis is the fundamental stage toward a number of mortal complications of liver diseases, including cirrhosis and hepatocellular carcinoma. Canonical Wnt pathway is crucial in diverse biological processes and mediates the progression and regression of liver fibrosis. As a potent Wnt pathway agonist, the role of roof plate-specific spondin-2 (R-Spondin2) in the hepatic fibrosis has not been well elucidated.
aimsThe purpose of this study was to investigate whether R-Spondin2 contributes to hepatic stellate cells (HSCs) activation, the key event in liver fibrogenesis.
methodsHuman liver tissues, hepatic fibrosis mouse model, and freshly isolated mice HSCs were used. Protein expression and transcriptional level were analyzed by Western-blot assays and real-time PCR, respectively. Exogenous stimulation with recombinant R-Spondin2 and knockdown of R-Spondin2 were performed to investigate functionality. Nuclear β-catenin level and T cell-specific transcription factors activity were analyzed, and HSC proliferation was tested by MTT assay.
resultsOverexpression of R-Spondin2 was observed in both human fibrotic liver tissues and hepatic fibrosis mouse model. Exogenous stimulation with R-Spondin2 in the freshly isolated mice HSCs induced a dose-dependent increase in Wnt pathway activities, HSC proliferation, and the expression of α-smooth muscle actin (α-SMA) and Collagen I. Additionally, Wnt pathway activities, HSC proliferation, and the expressions of α-SMA and Collagen I decreased in the R-Spondin2 knockdown HSCs.
conclusionsThese findings suggest that R-Spondin2 may promote HSC activation by enhancing the canonical Wnt pathway.
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