Kinetics of MMP-1 and MMP-3 produced by mast cells and macrophages in liver fibrogenesis of rat.
BACKGROUND
The involvement of whether macrophages and mast cells in the kinetics of matrix metalloproteinases-1 (MMP-1), MMP-3 and MMP-9, tissue inhibitors of metalloproteinases-1 (TIMP-1) and TIMP-2 in hepatic fibrosis/cirrhosis was examined.


METHODS
The MMPs and TIMPs were examined by histopathology, immunohistochemistry and immunoblotting using carbon tetrachloride-induced fibrotic rat liver.


RESULTS
MMP-1 increased in proportion to the development of fibrosis and reached maximum at week 14. In the first four weeks, MMP-3 expression was mainly observed in many hepatocytes. At week 8, the macrophages in the fibrous septa, as well as hepatocytes, expressed MMP-3. TIMP-1 and -2 progressively increased throughout the experimental periods. The MMP-1 expression in the mast cells, however, did not decrease the degree of liver cirrhosis.


CONCLUSIONS
MMP-1, TIMP-1 and -2 expressions increased in the late stages of fibrosis and cirrhosis. During recovery, the MMP-3 expression of macrophages greatly increased in the unresolved fibrous septa.
Jeong
Won-Il
WI
Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Do
Sun-Hee
SH
Jeong
Da-Hee
DH
Hong
Il-Hwa
IH
Park
Jin-Kyu
JK
Ran
Ki-Mi
KM
Yang
Hai-Jie
HJ
Yuan
Dong-Wei
DW
Kim
Soon-Bok
SB
Cha
Myung-Sook
MS
Jeong
Kyu-Shik
KS
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D005355:Fibrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D002251:Carbon Tetrachloride; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1