KMID : 0385020030190030176
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Korean Journal of Laboratory Animal Science 2003 Volume.19 No. 3 p.176 ~ p.185
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Cell Cycle Protein Profile of the Hepatocytes and Hepatic Stellate Cells in Dimethylnitrosamine-Induced Rat Hepatic Fibrosis
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Kim Mi-Rhan
Kim Han-Seong Lee Mi-Sook Park Soo-Young Jang Ja-June
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Abstract
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DMN(Dimethynitrosamine)-induced rat liver cirrhosis shares similar histological and serological features with human cirrhosis and is found to cause excessive deposition of extracellular matrix proteins. This animal model appears appropriate for the study of the early events associated with the development of hepatic fibrosis. There has been an extensive research focus in cell cycle control and relationship that exist between cellular proliferation and cancer. This study was designed to identify expression of cell cycle control proteins in hepatocytes and hepatic stellate cells, respectively, during DMN-induced rat hepatic fibrosis. Six-week-old female Sprague-Dawley rats were intraperitoneally injected 10 ¥ìl of DMN/ body weight, 3 consecutive days a week for 4 weeks. The animals were perfused at week 1, 2, 3, and 4 and purified hepatocytes and hepatic stellate cells in one animal. In the hepatocytes, CDK2 protein level was early elevated and then returned to that of the controls. The highest peak of CDK4 and cdc2 was seen at week 4. Cyclin A and cyclin B protein expressions had also risen at week 1, and remained high level but cyclin D is down regulated. In the hepatic stellate cells, expressions of CDK2, CDK4, cdc2, cyclin D and PCNA were all decreased. Apoptosis inhibiting protein, bcl-2, expression however increased from week 1 , and peaked at week 4. Expression of Fas rised at week 1 and peaked at week 2. The number of apoptotic cells was dramatically increased at week 1 but then decreased, again slightly increased at week 4. S-phase cells revealed a similar induction pattern to apoptosis. These results suggest that control mechanism of proliferation of hepatocytes and hepatic stellate cells during hepatic fibrogenesis differs each other.
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KEYWORD
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DMN, liver fibrosis, hepatic stellate cell, CDK, cyclin, apoptosis
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