Cited 0 times in Scipus Cited Count

Dimethylnitrosamine-Induced Liver Cirrhosis and Expression of Hepatocyte Growth Factor (HGF), its Receptor c-Met, and the Transforming Growth Factor (TGF)- β 1 in Sprague-Dawley Rats

Other Title
백서에서 Dimethylnitrosamine에 의한 간경화의 유도와 간세포성장인자, 수용체인 c-Met, 그리고 형질전환인자-베타 1의 발현에 관한 연구
Authors
김, 욱환  | 이, 재호  | 진, 윤미  | 조, 혜성  | 박, 혜리 | 정, 민권  | 곽, 연식 | 한, 상욱  | 왕, 희정  | 이, 건욱 | 김, 명욱
Citation
Journal of the Korean Surgical Society, 55(4). : 453-468, 1998
Journal Title
Journal of the Korean Surgical Society
ISSN
1226-0053
Abstract
BACKGROUND: Liver fibrosis and cirrhosis are the ultimate histologic consequences of chronic liver damage. Efforts have been made to study the mechanisms of cirrhosis and to discover effective therapeutic strategies. However, to date, no animal model reproduces the disease in man. The purpose of this work is to establish a model of DMN-induced liver cirrhosis for treatment of liver cirrhosis, to understand the basic characteristics of DMN-induced liver cirrhosis, and to confirm the expression of HGF, its receptor c-Met, and TGF-beta1 in Sprague-Dawley rats.
METHODS: Five-week-old male Sprague-Dawley rats (n=56) were used for this study. Liver cirrhosis was induced in the rats by using DMN (1 ml/kg body weight, i.p.) given 3 consecutive days a week for 6 weeks. Changes in the portal vein pressure were measured by a venous catheter during the duration of the DMN-treatment. The levels of serum albumin, bilirubin, and ammonia were determined in a clinical laboratory by routive methods. Pieces of the median lobe were cut and fixed in 10% buffered neutral formalin, embedded in paraffin, and stained by hematoxylin-eosin (H&E) & masson-trichrome (M&T). Changes in the extracellular matrix were measured by image analysis and hydroxyproline content. Immunohistochemical staining of alpa-smooth muscle actin was performed to confirm the activation ofhepatic stellate cells. Northern blot analyses were performed to confirm the expression of HGF and TGF-beta1 and western blotting was performed c-Met, HGF receptor.
RESULTS: Pressures in the portal vein were significantly increased during the DMN-treatment time (p<0.05). Biochemical parameters were significantly correlated with the progression of liver cirrhosis. H&E staining of 4-week DMN-treated rats demonstrated fibrous tissue bridging between the periportal and the pericentral areas with gradual widening of fibrous bands. Both the extracellular matrix measured by image analysis of the M&T staining and the hydroxyproline content rose continuously throughout the 6 weeks of DMN treatment. alpa-smooth muscle actin was observed in the stellate cells of DMN-treated rats. The northern blot analyses showed that the expression of HGF mRNA decreased with the progression of DMN-induced liver cirrhosis but that of TGF-beta1 mRNA did not. The western blot analyses showed that the expression of the c-Met receptor protein increased continuously, but the expression of HGF mRNA a decreased.
CONCLUSION: The model of cirrhosis induced by chronic, discontinuous treatment with a low dose of DMN in rats was simple and predictable and displayed many of the features of human cirrhosis. The decrease in the expression of HGF mRNA may be responsible for the reduced hepatocyte regeneration in liver cirrhosis. The expression of the c-Met protein was related with the decreased expression of HGF. The exact significance of TGF-beta1 was not determined in this study.
Keywords

Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Laboratory Medicine
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Ajou Authors
김, 명욱  |  김, 욱환  |  왕, 희정  |  이, 재호  |  정, 민권  |  조, 혜성  |  진, 윤미  |  한, 상욱
Full Text Link
Files in This Item:
There are no files associated with this item.
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse