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Emerging role of adipokine apelin in hepatic remodelling and initiation of carcinogensis in chronic hepatitis C patients.

Abstract

BACKGROUND

Although accumulating data has implicated a role for the Apelinergic system in cirrhosis, the role of Apelin during different stages of fibrogenesis has not been clarified, whereas no studies have been conducted on its expression in human hepatocellular carcinoma (HCC). This study aimed to elucidate its role in hepatic remodelling and carcinogenesis.

METHODS

Immunolocalization of Apelin was compared during different stages of HCV-induced liver disease (n=123).

RESULTS

Apelin level in hepatic stellate cells (HSC), portal fibroblast and endothelial cells was significantly elevated in F3 stage .In cirrhosis, the expression was markedly striking and extended as linear staining in the cirrhotic septa and proliferated capillaries. In liver cirrhosis with high grade dysplastic nodule (HGDN) group and liver cirrhosis with HCC group, Apelin was constantly expressed in the hepatocytes with the exemption of non-parenchymatous cells. Apelin gradually increased in HGDN, HCC grade-I and HCC grade II (P<0.0001). In contrast, Apelin gradually decreased in the cirrhosis adjacent to HGDN, HCC grade-I and HCC grade II (P<0.0001). The gradual incline in Apelin expression in dysplastic and malignant cells was paralleled by a decline in their adjacent cirrhotic liver (P=0.013).

CONCLUSION

In HCV chronic hepatitis, Apelin seems to manipulate the differentiation of HSC ending in hepatic remodelling. The uptake of Apelin from the stromal components by the epithelial cells may initiate the transformation of adjacent epithelial cells and supports the evolution and progression of dysplastic nodules and hepatocellular carcinoma. These findings could have both prognostic and therapeutic applications.

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  • Authors+Show Affiliations

    ,

    Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.

    ,

    Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.

    Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.

    Source

    MeSH

    Adult
    Aged
    Apelin
    Biopsy
    Carcinoma, Hepatocellular
    Cell Transformation, Viral
    Disease Progression
    Endothelial Cells
    Female
    Fibroblasts
    Hepatic Stellate Cells
    Hepatitis C, Chronic
    Humans
    Immunohistochemistry
    Intercellular Signaling Peptides and Proteins
    Liver
    Liver Cirrhosis
    Liver Neoplasms
    Male
    Middle Aged
    Signal Transduction

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    24966992

    Citation

    Farid, Rola M., et al. "Emerging Role of Adipokine Apelin in Hepatic Remodelling and Initiation of Carcinogensis in Chronic Hepatitis C Patients." International Journal of Clinical and Experimental Pathology, vol. 7, no. 5, 2014, pp. 2707-17.
    Farid RM, Abu-Zeid RM, El-Tawil A. Emerging role of adipokine apelin in hepatic remodelling and initiation of carcinogensis in chronic hepatitis C patients. Int J Clin Exp Pathol. 2014;7(5):2707-17.
    Farid, R. M., Abu-Zeid, R. M., & El-Tawil, A. (2014). Emerging role of adipokine apelin in hepatic remodelling and initiation of carcinogensis in chronic hepatitis C patients. International Journal of Clinical and Experimental Pathology, 7(5), pp. 2707-17.
    Farid RM, Abu-Zeid RM, El-Tawil A. Emerging Role of Adipokine Apelin in Hepatic Remodelling and Initiation of Carcinogensis in Chronic Hepatitis C Patients. Int J Clin Exp Pathol. 2014;7(5):2707-17. PubMed PMID: 24966992.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Emerging role of adipokine apelin in hepatic remodelling and initiation of carcinogensis in chronic hepatitis C patients. AU - Farid,Rola M, AU - Abu-Zeid,Riham M, AU - El-Tawil,Ahmed, Y1 - 2014/04/15/ PY - 2014/03/02/received PY - 2014/04/04/accepted PY - 2014/6/27/entrez PY - 2014/6/27/pubmed PY - 2015/2/24/medline KW - Apelin KW - HCV KW - cirrhosis KW - hepatocellular carcinoma KW - high grade dysplasia SP - 2707 EP - 17 JF - International journal of clinical and experimental pathology JO - Int J Clin Exp Pathol VL - 7 IS - 5 N2 - BACKGROUND: Although accumulating data has implicated a role for the Apelinergic system in cirrhosis, the role of Apelin during different stages of fibrogenesis has not been clarified, whereas no studies have been conducted on its expression in human hepatocellular carcinoma (HCC). This study aimed to elucidate its role in hepatic remodelling and carcinogenesis. METHODS: Immunolocalization of Apelin was compared during different stages of HCV-induced liver disease (n=123). RESULTS: Apelin level in hepatic stellate cells (HSC), portal fibroblast and endothelial cells was significantly elevated in F3 stage .In cirrhosis, the expression was markedly striking and extended as linear staining in the cirrhotic septa and proliferated capillaries. In liver cirrhosis with high grade dysplastic nodule (HGDN) group and liver cirrhosis with HCC group, Apelin was constantly expressed in the hepatocytes with the exemption of non-parenchymatous cells. Apelin gradually increased in HGDN, HCC grade-I and HCC grade II (P<0.0001). In contrast, Apelin gradually decreased in the cirrhosis adjacent to HGDN, HCC grade-I and HCC grade II (P<0.0001). The gradual incline in Apelin expression in dysplastic and malignant cells was paralleled by a decline in their adjacent cirrhotic liver (P=0.013). CONCLUSION: In HCV chronic hepatitis, Apelin seems to manipulate the differentiation of HSC ending in hepatic remodelling. The uptake of Apelin from the stromal components by the epithelial cells may initiate the transformation of adjacent epithelial cells and supports the evolution and progression of dysplastic nodules and hepatocellular carcinoma. These findings could have both prognostic and therapeutic applications. SN - 1936-2625 UR - https://www.unboundmedicine.com/medline/citation/24966992/Emerging_role_of_adipokine_apelin_in_hepatic_remodelling_and_initiation_of_carcinogensis_in_chronic_hepatitis_C_patients_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24966992/ DB - PRIME DP - Unbound Medicine ER -