Dynamic changes of typeⅠ,Ⅲand N collagen synthesis and distribution of collagen-producing cells in carbon tetrachloride-induced rat liver fibrosis

AIM To find out the relationship between the gene transcription of different types ofprocollagen and the deposition of the relevant collagens in the liver tissue and to confirm the types of collagen producing cells in liverfibrogenesis.METHODS Dynamic changes of the expression of α1(Ⅰ ), α1 (Ⅲ ) and α1 (Ⅳ) procollagen mRNAand relevant collagens and the distribution ofcollagen producing cells during liver fibrogenesis of rat induced by CCl4 (20 weeks)were investigated with Northern blot analysis,in situ hybridization and immunohistochemicaltechniques.RESULTS The increased expression of α1 (Ⅲ)procollagen mRNA by Northern blot analysis was the most predominant one among the threemRNAs during fibrogenesis. However, theenhanced expression of al (Ⅳ) procollagenmRNA occurred very early while the expressionof α1 (Ⅰ) mRNA was not enhanced much until themiddle stage of the exPeriment. D6smin (Dm)positive hepatic stellate cells (HSCs) and fewmyofibroblasts (MFs) in and around the necrotic areas expressed α1 (Ⅰ), α1 (Ⅲ) and α1 (Ⅳ)procollagen mRNA signals detected by in situhybridization at the early stage of theexperiment. All the three procollagen mRNAsignals thereafter mainly localized in fibroblasts (Fbs) and MFs in fibrotic septa during the middle and late stages of fibrosis, which distributedparallel to the corresponding collagens detected by immunohistochemical study. ln addition, the endothelial cells of sinusoids and the small blood vessels within the septa also showed α1(Ⅳ) procollagen mRNA and type Ⅳ collagen expressionCONCLUSION It is considered that "HSC-MF-Fb" effect cell system is the major cellularsource 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 fromMFs and Fbs, which play a very important role in the progress of liver fibrosis. The endothelialcells along sinusoids, as another source of Col Ⅳ production, might participate in the capillization of liver sinusoids.

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 expressionCONCLUSION 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.