[Aging changes of gelatinase activity in kidney tissue of autoimmune MRL/lpr mice].
OBJECTIVE
To determine whether increased expressions of gelatinases occur with aging in vivo in kidney tissue of autoimmune MRL/lpr mice by in situ zymography.


METHODS
MRL/lpr mice at the age of 8 weeks, 16 weeks and 24 weeks were investigated. Kidney protein extracts were compared for activities of MMP-2/9 by gelatin zymography. Immunohistochemistry and SDS-PAGE gelatin zymography were used to determine the expressions and activities of gelatinase A (MMP-2) and gelatinase B (MMP-9). To determine the net gelatinase activities in murine lupus kidney, in situ zymography was used with autoradiographic emulsion as substrate.


RESULTS
Both gelatinase A and B were seldom detected in the kidney tissue in 8 week old mice, Increased expressions of both latent and activated form enzymes of MMP-2/9 were identified in kidney extraction by SDS-PAGE gelatin zymography and immunohistochemical staining showed both MMP-2 and MMP-9 were obviously up-regulated within glomerulus as well as tubular-interstitium in mice at the age of 16 and 24 weeks. In situ zymography showed markedly increased gelatinase activities in kidney tissue consistent with the results of immunohistochemical staining, it is mainly derived from MMPs and inhibited by EDTA but not by PMSF or aprotinin.


CONCLUSIONS
These in vivo results suggested that MMP-2/-9 expressions were significantly up-regulated with aging in murine lupus nephritis, which may play an important role in promoting the remodeling formation of ECM and thus contribute to the progression of renal damage in this model.
Cai
Guangyan
G
Division of Nephrology, Kidney Center & Key Lab of Chinese PLA, General Hospital of Chinese PLA, Beijing 100853, China.
Chen
Xiangmei
X
Wang
Zhaoxia
Z
Tian
Yue
Y
Shi
Suozhu
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008181:Lupus Nephritis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D015854:Up-Regulation
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9