Fibrogenesis and Carcinogenesis in Nonalcoholic Steatohepatitis (NASH): Involvement of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinase (TIMPs)

Cancers

Isao Okazaki¹  Takuji Noro⁵  Nobuhiro Tsutsui⁵  Eigoro Yamanouchi²  Hajime Kuroda⁴  Masayuki Nakano³  Hiroaki Yokomori⁶ 

[1]Department of Internal Medicine, Sanno Hospital, International University of Health and Welfare, Tokyo 107-0052, Japan

[2]Department of Radiology, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan

[3] E-Mail:

[4]Department of Pathology, Ofuna Chuo Hospital, Kanagawa 247-0056, Japan

[5] E-Mail:

[6]Department of Pathology, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan

[7] E-Mail:

[8]Department of Surgery, International University of Health and Welfare Hospital, Tochigi 329-2763, Japan

[9] E-Mails:

[10]Department of Internal Medicine, Kitasato University Medical Center, Saitama 364-8501, Japan

[11] E-Mail:

关键词: hepatocellular carcinoma (HCC);    nonalcoholic steatohepatitis (NASH);    nonalcoholic fatty liver disease (NAFLD);    matrix metalloproteinase (MMP);    tissue inhibitor of metalloproteinase (TIMP);    cancer invasion;    cancer metastasis;    bone marrow-derived stem cell;    hepatic progenitor cell (HPC);    cancer stem cell;   

DOI  :  10.3390/cancers6031220

来源: mdpi

【 摘 要 】

Nonalcoholic steatohepatitis (NASH) is emerging worldwide because life-styles have changed to include much over-eating and less physical activity. The clinical and pathophysiological features of NASH are very different from those of HBV- and HCV-chronic liver diseases. The prognosis of NASH is worse among those with nonalcoholic fatty liver diseases (NAFLD), and some NASH patients show HCC with or without cirrhosis. In the present review we discuss fibrogenesis and the relationship between fibrosis and HCC occurrence in NASH to clarify the role of MMPs and TIMPs in both mechanisms. Previously we proposed MMP and TIMP expression in the multi-step occurrence of HCC from the literature based on viral-derived HCC. We introduce again these expressions during hepatocarcinogenesis and compare them to those in NASH-derived HCC, although the relationship with hepatic stem/progenitor cells (HPCs) invasion remains unknown. Signal transduction of MMPs and TIMPs is also discussed because it is valuable for the prevention and treatment of NASH and NASH-derived HCC.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.