[Effect of losartan on expression of Janus kinase 2 and signal transducer and activator of transcription 3 in glomeruli of diabetic rats].
OBJECTIVE
To investigate the effects of losartan on Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 in glomeruli of diabetic rats.


METHODS
Sixty Wistar male rats were randomly divided into control group (n=20), diabetes group (n=20), and losartan treatment group (n=20). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). Losartan (10 mg/kg) was administered daily by gavage from the day following the induction of diabetes. The animals were sacrificed in the weeks 2 and 4 after STZ injection. The renal cortical tissues were obtained and glomeruli were isolated. The protein expressions of JAK2, STAT3 and tyrosine phosphorylated STAT3 (p-STAT3) were assessed respectively by Western blot. Immunoprecipitation and Western blot analysis were used to determine tyrosine phosphorylated JAK2 (p-JAK2). JAK2 and STAT3 mRNA were assayed by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Compared with the control group rats, the respective expression of JAK2, p-JAK2, STAT3, p-STAT3, JAK2 mRNA and STAT3 mRNA was significantly increased in the diabetic glomeruli without losartan treatment (all P<0.01). After treatment with losartan, the expression of p-JAK2 and p-STAT3 in the diabetic glomeruli was down-regulated (all P<0.05). However losartan had no effect on the expression of JAK2, STAT3, JAK2 mRNA and STAT3 mRNA in the diabetic glomeruli.


CONCLUSIONS
JAK2 and STAT3 signal proteins may be involved in the kidney damage associated with diabetes. Regulation of phosphorylation of JAK2 and STAT3 may be responsible for the renal protective effects of losartan in diabetic rats.
Shi
Yong-hong
YH
Department of Pathology, Hebei Medical University, Shijiazhuang 050017, Hebei, China.
Duan
Hui-jun
HJ
He
Ning
N
Wang
Li-hui
LH
Liu
Qing-juan
QJ
Gao
Feng
F
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D019808:Losartan