Expression of tissue inhibitor of matrix metalloproteinase-1 in aging of transgenic mouse liver.
BACKGROUND
Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is related to the aging of many organs, but few data are available on the change of TIMP-1 in liver aging. The purpose of this study was to investigate the expression and role of TIMP-1, matrix metalloproteinase-2 (MMP-2) and MMP-9 in the process of natural aging in the livers of normal and transgenic mice, and to detect the effects of TIMP-1 on oxidative level and anti-oxidative ability of the livers of transgenic young mice.


METHODS
Normal and transgenic mice were divided into 3 groups according to their age: 3-month-old group (n = 5), 12-month-old group (n = 5) and 24-month-old group (n = 5). Histopathological changes of the liver were observed after HE and Masson staining. The messenger RNA (mRNA) levels of TIMP-1, MMP-2 and MMP-9 were determined by semi-quantitative reverse transcriptional polymerase chain reaction; protein expression was measured by Western blot in the livers of normal and transgenic mice of various ages. Changes in levels of superoxide dismutase (SOD), monoamine oxidase (MAO), malondialdehyde (MDA) as well as oxidative and anti-oxidative ability were measured.


RESULTS
Histologically, more fatty degeneration and collagen deposition were found in the aging livers of transgenic mice than in those of the normal mice as their age of months increased. The mRNA and protein expressions of TIMP-1 were significantly high in the oldest animals. The histopathological changes, mRNA and protein expressions of TIMP-1 increased significantly in the liver of transgenic mice as compared with normal mice. The expression of MMP-2 and MMP-9 showed a minor change in the process of aging. Liver change and collagen deposition were not observed in young mice, but the activity of SOD decreased (P < 0.05), and the activity of MAO (P < 0.01) and the content of MDA increased in the liver of transgenic mice (P < 0.01).


CONCLUSIONS
The expression of TIMP-1 is significantly high in the liver of transgenic mouse in the process of aging, indicating that the oxidative level increases and the anti-oxidative ability decreases in the liver of transgenic mouse. TIMP-1 plays an important role in the process of liver aging.
Department of Nephrology, General Hospital of PLA, Beijing 100853, China.
Yu-mei
YM
Zhang
Xiang-mei
XM
Chen
Di
D
Wu
Xue-guang
XG
Zhang
Yang
Y
Lü
Suo-zhu
SZ
Shi
Zhong
Z
Yin
D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019715:Tissue Inhibitor of Metalloproteinase-1; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9