| Thioacetamide 유발 간경변증에서 간섬유화정도와 Ito세포 및 RKC활성의 연관성 (The Relevance of Degree of Liver Fibrosis, Ito cell, and PKC Activity in Hepatic Fibrogenesis) |
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| The Relevance of Degree of Liver Fibrosis, Ito cell, and PKC Activity in Hepatic Fibrogenesis |
| Young Mi Jung, M.S., Kee Tack Jang, M.D., Yun Sil Lee1, Ph.D.,
In Kyoung Lim2, M.D., Mi Ran Kim, M.S., Min Jae Lee, Ph.D.,
Eui Keun Ham, M.D., Je G Chi, M.D., Jeong Wook Seo, M.D.,
In Ae Park, M.D., Chong Jai Kim, M.D., and Ja-June Jang, M.D. |
| Department of Pathology, Seoul National University College of Medicine, Laboratory of Radiation Effect, Korea Cancer Center Hosp ital1, Department of Biochemistry, Aoju University College of Medicine 2 |
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| ABSTRACT |
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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 event uallyleads 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 . Met hods : 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 αshowed no difference in TAA- treated group and control group. In TAA-treated group, PKCβ1 exhibited increased level of expression in both particulate and cytosolic forms at 9 weeks , while PKCδand PKC εshowed striking shift to particulated form. After 20 weeks, all of the PKC β1, δ, and εdegenerated and showed remarkably decreased level of expression. This suggested PKC αhad no relation to hepatic fibrosis,while PKC β1, δ, and ε, 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 β1, δ, and ε, 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.(Korean J Hepatol 1998;4:381 392) |
| KeyWords:
TAA, Liver fibrosis, Ito cell, Collagen content, PKC isoform |
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