Osteopontin expression in the liver with severe perisinusoidal fibrosis: autopsy case of Down syndrome with transient myeloproliferative disorder.
Down syndrome with transient myeloproliferative disorder (TMD) is often associated with perinatal liver fibrosis. The authors recently encountered an autopsy case of this disease with a characteristic severe perisinusoidal liver fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse fibro-inflammatory diseases. The purpose of the present report was to examine the involvement of OPN in development of the Down syndrome-associated liver fibrosis. Histology indicated severe perisinusoidal fibrosis and ductular arrangements of hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a feature of TMD associated with Down syndrome, was not evident. On immunohistochemistry expression of OPN was observed in hepatocytes often having ductular arrangements and infiltrating macrophages. In contrast, a small number of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were present in the liver. Numerous activated hepatic stellate cells (HSC) expressing alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A recent report indicated that OPN could directly activate the HSC. Thus, it is suggested that OPN produced by hepatocytes and macrophages induces activation of the HSC, and leads to the development of perisinusoidal liver fibrosis.
Tokairin
Takuo
T
Department of Pathology and Immunology, Division of Molecular Pathology and Tumor Pathology, Akita University School of Medicine, Akita, Japan.
Nishikawa
Yuji
Y
Watanabe
Hitoshi
H
Doi
Yuko
Y
Omori
Yasufumi
Y
Yoshioka
Toshiaki
T
Yamamoto
Youhei
Y
Yoshida
Masayuki
M
Nishimura
Takuya
T
Li
Qinchang
Q
Arai
Hirokazu
H
Ishida
Akira
A
Takada
Goro
G
Enomoto
Katsuhiko
K
D001344:Autopsy; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000378:metabolism*; D053495:Osteopontin / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D053773:Transforming Growth Factor beta1; D053495:Osteopontin