Copyright
©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 7, 2009; 15(41): 5193-5199
Published online Nov 7, 2009. doi: 10.3748/wjg.15.5193
Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis
Mitsuteru Kitade, Hitoshi Yoshiji, Ryuichi Noguchi, Yasuhide Ikenaka, Kosuke Kaji, Yusaku Shirai, Masaharu Yamazaki, Masahito Uemura, Junichi Yamao, Masao Fujimoto, Akira Mitoro, Masahisa Toyohara, Masayoshi Sawai, Motoyuki Yoshida, Chie Morioka, Tatsuhiro Tsujimoto, Hideto Kawaratani, Hiroshi Fukui
Mitsuteru Kitade, Hitoshi Yoshiji, Ryuichi Noguchi, Yasuhide Ikenaka, Kosuke Kaji, Yusaku Shirai, Masaharu Yamazaki, Masahito Uemura, Junichi Yamao, Masao Fujimoto, Akira Mitoro, Masahisa Toyohara, Masayoshi Sawai, Motoyuki Yoshida, Chie Morioka, Tatsuhiro Tsujimoto, Hideto Kawaratani, Hiroshi Fukui, Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan
Author contributions: Kitade M and Yoshiji H acquired the clinical cases and patient consent, conceived the study, participated in its design, assisted in data collection, coordinated and helped draft the manuscript; Yoshiji H undertook the literature search and contributed to the writing and article review; Noguchi R, Ikenaka Y, Kaji K, Shirai Y, Yamazaki M, Uemura M, Yamao J, Fujimoto M, Mitoro A, Toyohara M, Sawai M, Yoshida M, Morioka C, Tsujimoto T, Kawaratani H and Fukui H were responsible for diagnosis, patient management and review; all authors read and approved the final manuscript.
Correspondence to: Dr. Hitoshi Yoshiji, Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
Telephone: +81-744-223051 Fax: +81-744-247122
Received: August 24, 2009
Revised: September 19, 2009
Accepted: September 26, 2009
Published online: November 7, 2009
AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).
METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18-immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.
RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18 expression and HOMA-R were significantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization.
CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.
