Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection

Autor:	Koichi Matsuzaki, Katsunori Yoshida, Q. L. Jin, Miki Murata, J. Q. Niu, Koichi Tsuneyama, Yuki Moritoki, Zhe-Xiong Lian, Takashi Yamaguchi, Y.-R. Deng
Rok vydání:	2014
Předmět:	Adult Liver Cirrhosis Male Hepatitis B virus Carcinoma Hepatocellular Cirrhosis Immunology medicine.disease_cause Antiviral Agents Young Adult Liver disease Hepatitis B Chronic Fibrosis Telbivudine medicine Humans Protein Isoforms Immunology and Allergy Smad3 Protein Phosphorylation Nucleoside analogue business.industry Kinase Liver Neoplasms Lamivudine Middle Aged medicine.disease Immunohistochemistry digestive system diseases Treatment Outcome Liver DNA Viral Disease Progression Hepatocytes Female Original Article business Signal Transduction Thymidine medicine.drug
Zdroj:	Clinical and Experimental Immunology. 176:102-111
ISSN:	1365-2249 0009-9104
DOI:	10.1111/cei.12259
Popis:	Summary Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1–4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc93a0d7fa8fd34740231b19400cddbc https://doi.org/10.1111/cei.12259 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.