Korean J Hepatol.  1998 Dec;4(4):381-392.

The Relevance of Degree of Liver Fibrosis, Ito cell, and PKC Activity in Hepatic Fibrogenesis

• Jung YM
• Jang KT
• Lee YS
• Lim IK
• Kim MR
• Myoung NK
• Lee MJ
• Jang JJ

Abstract

BACKGROUND/AIMS
Hepatic fibrosis in rat induced by thioacet amide shares similar morphological and biochemical characteristics with human liver cirrhosis. Thioacetamide (T AA) initially induces accumulation of collagen in Disse space and eventually leads to macro- and micronodular cirrhos is. Ito cell was believed to play a main role in hepatic fibrosis. And it s activity was known to be regulated by the expression of various genes. But little has been discovered about the upstream signal trans duction pathway of these genes in hepatic fibrosis. The expression of genesrelated to Ito cell activity was regulated by many transcription factors , the activity of which was regulated by protein kinase C( PKC) is oforms. So it is s upposed that PKC could be as s ociated with fibrosis in liver.
METHODS
We investigated the correlation of PKC is oforms and It ocell activity in the course of hepatic fibrosis using TAA induced rat liver cirrhosis model. We used six week- old male rats , and administered 0.03% TAA in drinking water. The animals were sacrificed at 9, 20, and 30 weeks after TAA administration. The degree of hepatic fibrosis was evaluated by measuring the total amount of collagen.-SMA immunohist ochemical st aining of liver tissue was done to determine the Ito cell activity. The expression pattern of PKC isoforms was investigated by West ern blotting.
RESULTS
In TAA- treated group, collagen cont ent and Ito cell activity did not increase until 30 weeks and 20 weeks of treatment , respectively, while in control group collagen cont ent and Ito cell activity were not detected. Collagen content showed linear correlation with Ito cell activity. This implied that the proliferation of activated Ito cells was prior to the increase of collagen content. In view of expression pattern of PKC is oforms, PKC alpha showed no difference in TAA- treated group and control group. In TAA-treated group, PKCbeta1 exhibited increased level of expression in both particulate and cytosolic forms at 9 weeks, while PKCdelta and PKC epsilon showed striking shift to particulated form. After 20 weeks, all of the PKC beta1, delta, and epsilon degenerated and showed remarkably decreased level of expression. This suggested PKC alpha had no relation to hepatic fibrosis,while PKC beta1, delta, and epsilon, showing activity at 9 weeks, were related to fibrosis og liver. In response to fibrogenic factors, molecules engaged in intracellular signal transduction pathway like PKC beta1, delta, and epsilon, began to change prior to the increase of Ito cell activity, morphologic changes and alterations of collagen content.
CONCLUSION
Our results strongly suggest that the activity of PKC isoforms play an important role in early step of hepatic fibrosis, while accompanying Ito cell activity do in later step.

Keyword

TAA; Liver fibrosis; Ito cell; Collagen content; PKC isoform

MeSH Terms

Animals
Collagen
Cytosol
Drinking Water
Fibrosis
Hepatic Stellate Cells
Humans
Liver Cirrhosis*
Liver*
Male
Protein Isoforms
Protein Kinase C-epsilon
Protein Kinases
Rats
Signal Transduction
Strikes, Employee
Thioacetamide
Transcription Factors
Collagen
Drinking Water
Protein Isoforms
Protein Kinase C-epsilon
Protein Kinases
Thioacetamide
Transcription Factors