| Abstract | Dimethylnitrosamine administration induces a rapid increase in collagen deposition with concomitant proliferation of hepatic stellate cells in rats. Here, we investigated the pathophysiological profiles of acute and chronic hepatic fibrosis states and attempted to determine the possible role of Kruppel-like factor-5 (KLF5) in this model. In acute study using a single drug injection, we observed a rapid transient increase of ALT and mRNA levels of KLF5 followed by increases in fibrosis-related genes. Repeated administration of dimethylnitrosamine once a week caused early damage with severe fibrosis and sustained hepatocyte injury, while intermittent injections at 2-week intervals induced only modest fibrosis from 3 weeks. Weekly administration also induced profound upregulation of collagen I, alpha-smooth muscle actin, and KLF5 mRNA. In contrast, such continued augmentation was not observed after intermittent injections; KLF5 increased only after 3 weeks. These results suggested that dimethylnitrosamine induced a rapid hepatic fibrogenic response with a possible participation of KLF5. |
| Authors | Fumihiro Ohara, Aisuke Nii, Yojiro Sakiyama, Megumi Tsuchiya, Shinji Ogawa
(Affiliation: St Louis Laboratories, Pfizer Global Research and Development, Chesterfield, MO 63017, USA. fohara at asahi.email.ne.jp)
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| Journal | Digestive diseases and sciences
(Dig Dis Sci)
Vol. 53
Issue 8
Pg. 2222-32
(Aug 2008)
ISSN: 0163-2116 United States |
| PMID | 18095165
(Publication Type: Journal Article)
|
| Chemical References |
- Actins
- Collagen Type I
- Klf5 protein, rat
- Kruppel-Like Transcription Factors
- RNA, Messenger
- smooth muscle actin, rat
- Dimethylnitrosamine
- Alanine Transaminase
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| Topics |
- Actins
(metabolism)
- Acute Disease
- Alanine Transaminase
(metabolism)
- Animals
- Chronic Disease
- Collagen Type I
(metabolism)
- Dimethylnitrosamine
- Disease Models, Animal
- Kruppel-Like Transcription Factors
(genetics, metabolism)
- Liver
(enzymology, metabolism, pathology)
- Liver Cirrhosis
(chemically induced, metabolism, pathology)
- Male
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Time Factors
- Up-Regulation
|
