ArticleBMC research notes2012
Gremlin in the pathogenesis of hepatocellular carcinoma complicating chronic hepatitis C: an immunohistochemical and PCR study of human liver biopsies.
Article in BMC research notes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Serum Gremlin 1 Remains Elevated Following Successful Direct-Acting Antiviral Therapy for Chronic Hepatitis C.Viruses · 2026Article
- Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways.Cells · 2022Article
- Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4.Drug target insights · 2020Article
- Decreased BMP-7 and p-Smad1/5/8 expression, and increased levels of gremlin in hepatocellular carcinoma.Oncology letters · 2018Article
- BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration.International journal of molecular sciences · 2017Review
- Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats.The journal of headache and pain · 2017Article
- Gremlin1 plays a key role in kidney development and renal fibrosis.American journal of physiology. Renal physiology · 2017Article
- Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma.Journal of gastroenterology · 2017Review
- Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster.Oncotarget · 2016Article
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Authors and funding
5 authors.
Funding
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Abstract
backgroundThe possible role of secretory products of fibrous tissue in the development of hepatocellular carcinoma (HCC) complicating chronic hepatitis C was investigated. Our hypothesis was that gremlin, secreted by fibroblasts, inhibited bone morphogenic protein (BMP), which mediates stem cell maturation into adult functioning hepatocytes, and thus, arrest stem cell maturation and promoted their proliferation in an immature state possibly culminating into development of HCCs.
resultsProtein expression of cytokeratin 19 (CK19) and fibroblast growth factor 2 (FGF-2), and mRNA expression of gremlin and BMP-7 were studied in 35 cases of chronic hepatitis, cirrhosis and HCC complicating chronic hepatitis C. CK19 expression was higher in cases of cirrhosis (0.004), which correlated with the grade (r = 0.64, p = 0.009) and stage (r = 0.71, p = 0.001). All HCCs were negative for CK19. Stem cell niche activation (as indicated as a ductular reaction) was highest in cases of cirrhosis (p = 0.001) and correlated with CK19 expression (r = 0.42, p = 0.012), the grade(r = 0.56, p = 0.024) and stage (0.66, p = 0.006). FGF-2 expression was highest in HCCs and correlated with the grade (r = 0.6, p = 0.013), stage (0.72, p = 0.002), CK19 expression (r = 0.71, p = 002) and ductular reaction (0.68, p = 0.004) in hepatitis cases. Higher numbers of cirrhosis cases and HCCs (p = 0.009) showed gremlin expression, which correlated with the stage (r = 0.7, p = 0.002). Gremlin expression correlated with that of CK19 (r = 0.699, p = 0.003) and FGF2 (r = 0.75, p = 0.001) in hepatitis cases.
conclusionsFibrosis promotes carcinogenesis by fibroblast-secreted gremlin that blocks BMP function and promotes stem cell activation and proliferation as well as possibly HCC development.
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