Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.
OBJECTIVE
The aim of this study was to investigate whether both matrix metalloproteinase-2 (MMP-2) and membrane type 1 MMP (MT1-MMP) participate in the spontaneous resolution of liver fibrosis.


METHODS
Transcription of both genes was examined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Gelatinase activity was investigated by zymography.


RESULTS
Gene expression by RT-PCR showed that both genes increased in the process of liver fibrosis, then decreased gradually in the recovery phase. ISH revealed that distribution of positive cells changed quickly in the recovery phase. Positive cells were widely seen in the liver, mainly around fibrous septa, in the aggressive phase, but were exclusively observed at the interface between the resolving fibrous band and the parenchyma, then were diffusely located in the lobules in the recovery phase. Main cells expressing both mRNAs seemed to be stellate cells for their morphology, though they did not express characteristic cell markers. Some hepatocytes and Kupffer cells expressed both mRNAs in the recovery phase. Gelatinase activity of MMP-2 increased in the recovery phase of 8-week-treated rat liver by gelatin zymography.


CONCLUSIONS
The results of present study suggest that both enzymes participate in the destruction of extracellular matrix in coordination with MMP-13.
Watanabe
T
T
Department of Environmental Health, Tokai University School of Medicine, Isehara, Kanagawa, Japan. tewatana@is.icc.u-tokai.ac.jp
Niioka
M
M
Ishikawa
A
A
Hozawa
S
S
Arai
M
M
Maruyama
K
K
Okada
A
A
Okazaki
I
I
D000818:Animals; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2