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Journal of Histochemistry and Cytochemistry, Vol. 51, 1139-1149, September 2003, Copyright © 2003, The Histochemical Society, Inc.

ARTICLE

Immunohistochemical Localization of Hepatocyte Growth Factor Activator (HGFA) in Developing Mouse Liver Tissues: Heterogeneous Distribution of HGFA Protein

Ichiei Iidaa, Kohei Johkurab, Ruifeng Tenga, Suguru Kubotaa, Li Cuia, Xu Zhaoa, Naoko Ogiwarab, Yasumitsu Okouchib, Kazuhiko Asanumab, Jun Nakayamac, and Katsunori Sasakia,b
a Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine
b Department of Anatomy and Organ Technology, Shinshu University School of Medicine, Matsumoto, Japan
c Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan

Correspondence to: Ichiei Iida, Inst. of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. E-mail: i2davh@coral.ocn.ne.jp

Hepatocyte growth factor activator (HGFA) can activate the single-chain hepatocyte growth factor (HGF) required for embryonic development. We studied the immunohistochemical (IHC) localization of HGFA in adult mouse liver and its developmental changes from embryonic day 12 to postnatal day 30. A heterogeneous distribution of HGFA was observed in adult liver tissues. The hepatocytes around the hepatic veins were preferentially positive for HGFA, whereas those in other areas were negative. Depending on the vascular diameter, the hepatic veins were bordered by a one- to three-cell-thick layer of hepatocytes positive for HGFA, which showed evidence of cell–cell heterogeneity in staining intensity. Immunoelectron microscopy detected ubiquitous distribution of the gold particle reaction product for HGFA in the cytoplasm of these hepatocytes, especially in the rough endoplasmic reticulum. Developmental analysis indicated that there was hardly any staining of HGFA until postnatal day 0 and that noticeable staining was initially detected in the pericentral hepatocytes on postnatal day 3. Subsequently, immunoreactivity increased and the distinct staining pattern had been established by postnatal day 30. These results suggest that HGFA proteins are produced in the hepatocytes surrounding the efferent hepatic veins in the mouse and that development of the unique distributing pattern takes place postnatally. (J Histochem Cytochem 51:1139–1149, 2003)

Key Words: hepatocyte growth factor, activator, liver, development, immunohistochemistry, mouse


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