[Losartan downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat].
OBJECTIVE
To investigate the influence of losartan on the expression of transforming growth factor-beta type I and type II receptors (TGF beta RI, TGF beta RII) in kidney of diabetic rat model.


METHODS
The Wistar rats were randomly divided into 3 groups with 10 rats in each group: normal control group (group C), diabetic rat model group (group DM, the model was reproduced by intravenous injection of 50 mg/kg streptozotocin), and the group of diabetic rat model treated with losartan (group DL, 10 mg.kg(-1).d(-1) of losartan intragastrically since the 2nd day of streptozotocin injection). Eight weeks later, the mRNA and protein expressions of TGF beta RI, TGF beta RII and fibronectin in renal cortices of all 3 groups were measured by semiquantitative reverse transcription-polymerase chain reaction and by histoimmunochemical methods. The blood glucose, urea and creatinine were detected by biochemical assay and the blood insulin and angiotensin II by radioimmunoassay. The urine albumin excretion ratio was examined by sulfosalicylic acid assay.


RESULTS
The mean glomerular volume, kidney weight/body weight ratio, urine albumin excretion ratio, blood urea and creatinine were significantly elevated in group DM than that in group C (P < 0.05). The mRNA and protein expressions of TGF beta RI, TGF beta RII and fibronectin in renal cortices of group DM were significantly increased than that in group C as well (P < 0.05). The increase in mean glomerular volume, kidney weight/body weight ratio, urine albumin excretion ratio, blood urea and creatinine in group DL was significantly attenuated as compared to group DM. The mRNA and protein expressions of TGF beta RI, TGF beta RII and fibronectin in renal cortices of group DL were also significantly reduced as compared to that in group DM (P < 0.05).


CONCLUSIONS
Losartan may have protective effects on the kidney of diabetic rat model. The mechanism of the protection might related to its downregulatory effect on the expression of TGF beta system, which inhibited the hypertrophy of kidney cells and reduced the synthesis of extracellular matrix.
Guo
Zhi-xin
ZX
Department of Endocrinology, First Affiliated Hospital, Tianjin Medical University, Tianjin 300052, China.
Qiu
Ming-cai
MC
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015536:Down-Regulation; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005353:Fibronectins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D019808:Losartan