[Effects of losartan on MT3-MMP and TIMP2 mRNA expressions in diabetic rat kidney].
OBJECTIVE
To investigate the changes of the mRNA expressions of membrane type 3-matrix metalloproteinase (MT3-MMP) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2) in diabetic rat kidneys and the effect of losartan on such changes.


METHODS
Three groups of male Wistar rats were used in this study, namely group A as the control group (n=11), group B consisting of diabetic rats without any therapy (n=11), and group C treated with losartan (n=9). Six months after treatment, the kidneys were taken from the rats to measure the mRNA expressions of MT3-MMP, TIMP2 and transforming growth factor beta1eTGFbeta1 with reverse transcriptional PCR (RT-PCR), and observe the glomerular basement membrane thickening and mesangial matrix MMedensity (MM area/mesangial area) with electron microscope. Twenty-four-hour urine was also collected to measure urinary albumin excretion (UAE).


RESULTS
The expression of renal MT3-MMP mRNA in group B (1.37+/-0.96) was significantly stronger than those in group A (0.75+/-0.34, P<0.05) and in group C (0.75+/-0.30, P<0.05). The mRNA expression of renal TIMP2 in group B (0.73+/-0.37) was significantly increased as compared with group A (0.32+/-0.19, P<0.05) and group C (0.34+/-0.17, P<0.05), with a higher mRNA expression of renal TGFbeta1 in group B (0.53+/-0.20 vs 0.26+/-0.13 in group A and 0.29+/-0.15 in group C, P<0.05). UAE in group B (2.18+/-1.98 mg) was significantly higher than those in groups A and C (0.41+/-0.47 mg/d, P<0.05; 0.65+/-0.89 mg/d, P<0.05, respectively). The glomerular basement membrane thickness (532+/-108 nm) and the MM density (56.4+/-6.8) were significantly greater in group Bthan in the other two groups (P<0.05).


CONCLUSIONS
MT3-MMP and the TIMP2 mRNA expressions are significantly increased in diabetic rat kidneys. Losartan can prevent the development of diabetic nephropathy and inhibit MT3-MMP and the TIMP2 mRNA expressions in diabetic rat kidneys.
Wan
Xia
X
Department of Nephrology, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Huang
Hu-hui
HH
Li
Jing-gao
JG
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D053513:Matrix Metalloproteinase 16 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000235:genetics
D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D053513:Matrix Metalloproteinase 16; D019808:Losartan