Original Articles
Copyright ©The Author(s) 1999. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 15, 1999; 5(5): 397-403
Published online Oct 15, 1999. doi: 10.3748/wjg.v5.i5.397
Dynamic changes of type I, III and IV collagen synthesis and distribution of collagen-producing cells in carbon tetrachloride-induced rat liver fibrosis
Wei-Dong Du, Yue-E Zhang, Wei-Rong Zhai, Xiao-Mei Zhou
Wei-Dong Du, Yue-E Zhang, Wei-Rong Zhai, Department of Pathology, Shanghai Medical University, Shanghai 200032, China
Xiao-Mei Zhou, National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute
Wei-Dong Du, male, born on 1958-11-11, got a doctorate degree in 1996 in Shanghai Medical University and now is working as a postdoctorate in Department of Molecular Biology of Max-Plank-Institute for Biochemistry, Germany, having 35 papers published.
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China (No.3933140) and Shanghai Municipal Education Commission (No.980802).
Correspondence to: Professor Yue-E Zhang M.D., Department of Pathology, Shanghai Medical University, 138 Yixueyuan Road, Shanghai 200032, China. zdxu@shmu.edu.cn
Telephone: +86·21·6404 1900 Ext. 2540 Fax: +86·21·6403 9987
Received: April 28, 1999
Revised: August 12, 1999
Accepted: September 20, 1999
Published online: October 15, 1999

AIM: To find out the relationship between the gene transcription of different types of procollagen and the deposition of the relevant collagens in the liver tissue and to confirm the types of collagen producing cells in liver fibrogenesis.

METHODS: Dynamic changes of the expression of α1(I), α1(III) and α1(IV) procollagen mRNA and relevant collagens and the distribution of collagen producing cells during liver fibrogenesis of rat induced by CCl4 (20 weeks) were investigated with Northern blot analysis, in situ hybridization and immunohistochemical techniques.

RESULTS: The increased expression of α1(III) procollagen mRNA by Northern blot analysis was the most predominant one among the three mRNAs during fibrogenesis. However, the enhanced expression of α1(IV) procollagen mRNA occurred very early while the expression of α1(I) mRNA was not enhanced much until the middle stage of the experiment. Desmin (Dm) positive hepatic stellate cells (HSCs) and few myofibroblasts (MFs) in and around the necrotic areas expressed α1(I), α1(III) and α1(IV) procollagen mRNA signals detected by in situ hybridization at the early stage of the experiment. All the three procollagen mRNA signals thereafter mainly localized in fibroblasts (Fbs) and MFs in fibrotic septa during the middle and late stages of fibrosis, which distributed parallel to the corresponding collagens detected by immunohistochemical study. In addition, the endothelial cells of sinusoids and the small blood vessels within the septa also showed α1(IV) procollagen mRNA and type IV collagen expression

CONCLUSION: It is considered that “HSC-MF-Fb” effect cell system is the major cellular source of collagen production in liver fibrosis, in which HSCs are collagen producing precursor cells in the early liver fibrogenesis, thereafter the synthesis of type I, III and IV collagens (Col I, Col III and Col IV) mainly derives from MFs and Fbs, which play a very important role in the progress of liver fibrosis. The endothelial cells along sinusoids, as another source of Col IV production, might participate in the capillization of liver sinusoids.

Keywords: Procollagen mRNA, immunohistochemistry, Northern blot analysis, in situ hybridization, liver fibrosis