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Immunohistochemical localization of truncated midkine in developing human bile ducts
1Second Department of Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan. makato@grape.med.tottori-u.ac.jp
Abstract:
Midkine (MK) is a heparin-binding growth factor whose gene has been identified in embryonal carcinoma cells in early stages of retinoic acid-induced differentiation. In the present study, we investigated the developmental localization of truncated MK protein in human bile ducts. Thirty specimens of the livers from 25 fetuses (from 9 to 40 gestational weeks) and from five neonates less than 4 weeks old were examined. Immunohistochemical analysis was performed using a mouse IgG2b monoclonal antibody against recombinant-truncated MK. Truncated MK was expressed moderately in the fetal liver from 9 to 15 gestational weeks. The immunoreactivities were found in the primitive hepatocytes, ductal plates, migrating biliary cells and immature bile ducts. The reaction products were localized in the cytoplasm heterogeneously. The intensity of immunostaining was weak from 15 gestational weeks to 26 gestational weeks. After 27 gestational weeks, truncated MK was not detected in the fetal livers. It was suggested that primitive hepatocytes, ductal plates and immature bile ducts produced truncated MK transiently during human bile ducts development.
Insights
Truncated midkine (MK) protein is transiently expressed in developing human bile ducts, appearing in primitive hepatocytes and immature bile ducts during early fetal development. This expression is not detected after 27 gestational weeks.
Area of Science:
- Developmental Biology
- Hepatology
- Cell Biology
Background:
- Midkine (MK) is a heparin-binding growth factor involved in cell growth and differentiation.
- Previous studies identified MK in embryonal carcinoma cells during retinoic acid-induced differentiation.
Purpose of the Study:
- To investigate the developmental localization of truncated MK protein in human bile ducts.
- To understand the role of MK during bile duct development.
Main Methods:
- Immunohistochemical analysis using a monoclonal antibody against truncated MK.
- Examination of 30 human fetal liver specimens (9-40 gestational weeks) and 5 neonatal liver specimens (<4 weeks old).
Main Results:
- Truncated MK was moderately expressed in fetal livers from 9 to 15 gestational weeks.
- Immunoreactivity was observed in primitive hepatocytes, ductal plates, migrating biliary cells, and immature bile ducts.
- Expression intensity decreased from 15 to 26 gestational weeks, and truncated MK was undetectable after 27 gestational weeks.
Conclusions:
- Truncated MK is transiently produced by primitive hepatocytes, ductal plates, and immature bile ducts during human bile duct development.
- MK expression appears to be a temporary event crucial for early bile duct formation.