Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis.
OBJECTIVE
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.


CONCLUSIONS
These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.
Kitade
Mitsuteru
M
Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan.
Yoshiji
Hitoshi
H
Noguchi
Ryuichi
R
Ikenaka
Yasuhide
Y
Kaji
Kosuke
K
Shirai
Yusaku
Y
Yamazaki
Masaharu
M
Uemura
Masahito
M
Yamao
Junichi
J
Fujimoto
Masao
M
Mitoro
Akira
A
Toyohara
Masahisa
M
Sawai
Masayoshi
M
Yoshida
Motoyuki
M
Morioka
Chie
C
Tsujimoto
Tatsuhiro
T
Kawaratani
Hideto
H
Fukui
Hiroshi
H
D000328:Adult; D016022:Case-Control Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D053538:Keratin-18 / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*
D053538:Keratin-18