Abnormal gene expression of matrix metalloproteinases and their inhibitor in glomeruli from diabetic rats.
The steady state levels of mRNA encoding for metalloproteinase (MMP)-1, -2, -3, and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 were examined in glomeruli at 4, 12, and 24 weeks after the injection of streptozocin (STZ) in rats. The mRNA levels for MMP-1 and MMP-3 decreased with age in STZ-induced diabetes. At 24 weeks after STZ injection, mRNA levels for MMP-1 and MMP-3 fell to 40% (p < 0.01) and 20% (p < 0.01), respectively, in the glomeruli of diabetic rats when compared with control rats. In contrast, mRNA levels for TIMP-1 increased significantly with age in the diabetic glomeruli and reached an 8-fold (p < 0.01) increased at 24 weeks after STZ injection. mRNA levels for MMP-2 were not altered in glomeruli from diabetic and control rats throughout the experimental period, whereas those for MMP-9 were not detected in glomeruli from either group of rats. Insulin treatment partially ameliorated the decrease in mRNA levels for MMP-1 and MMP-3 and the increase in those for TIMP-1 in the glomeruli of diabetic rats. These data indicate that abnormal gene regulation of MMPs and TIMP-1 in the glomeruli of diabetic rats may contribute to the progression of glomerular lesions and that hyperglycemia or insulin deficiency may be associated with abnormal MMPs and TIMP-1 gene regulation.
Nakamura
T
T
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Fukui
M
M
Ebihara
I
I
Osada
S
S
Tomino
Y
Y
Koide
H
H
D000818:Animals; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D007328:Insulin; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D008666:Metalloendopeptidases