[Effects of losartan on expressions of plasminogen activator and plasminogen activator inhibitor-1 of rat proximal tubular epithelial cells cultured with high glucose].
OBJECTIVE
To investigate the effects of high glucose on expressions of plasminogen activator (PA) and plasminogen activator inhibitor-1 (PAI-1) of rat proximal tubular epithelial cells, and the role of angiotensin II receptor antagonist Losartan.


METHODS
The cultured NRK-52E cells (a renal proximal tubular epithelial cell line of rat origin) were divided into five groups: control group, mannitol group (5 mmol/L D-glucose plus 25 mmol/L mannitol), high glucose group (30 mmol/L D-glucose), losartan group (10(-3) mmol/L losartan), high glucose plus losartan group (30 mmol/L D-glucose plus 10(-3) mmol/L losartan). Semi-quantity RT-PCR was used to detect the expression of PA/PAI-1 mRNA.


RESULTS
Compared with control group, the high glucose group decreased the expressions of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) mRNAs (P < 0.01) and increased PAI-1 mRNA expression (P < 0.01) in cultured NRK-52E cells. Losartan could reverse partly the expression of PA/PAI-1 mRNA. Compared to high glucose group, the PA mRNA expression was significantly increased (P < 0.01) and the PAI-1 mRNA expression was decreased greatly (P < 0.01) to high glucose plus losartan group.


CONCLUSIONS
The abnormal expression of PA/PAI-1 mRNA may play an important role in the accumulation of extracellular matrix (ECM) of diabetic nephropathy (DN). Losartan may keep the balance of PA/PAI-1 and have a protective effect on DN.
Pu
Li-jun
LJ
Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.
Huang
Song-min
SM
Liu
Fei
F
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D019808:Losartan / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D017395:Plasminogen Activator Inhibitor 1; C547314:Serpine1 protein, rat; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D005947:Glucose; D019808:Losartan