Sex-Differences in Renal Expression of Selected Transporters and Transcription Factors in Lean and Obese Zucker Spontaneously Hypertensive Fatty Rats

被引：13
作者：
Babelova, Andrea [1 ,2 ]
Burckhardt, Birgitta C. [3 ]
Wegner, Waja [3 ]
Burckhardt, Gerhard [3 ]
Henjakovic, Maja [3 ]
机构：
[1] Goethe Univ Frankfurt, Fac Med, Inst Cardiovasc Physiol 1, D-60596 Frankfurt, Germany
[2] Slovak Acad Sci, Inst Canc Res, Bratislava 83391, Slovakia
[3] Univ Med Ctr Gottingen, Inst Syst Physiol & Pathophysiol, D-37073 Gottingen, Germany
来源：
JOURNAL OF DIABETES RESEARCH | 2015年 / 2015卷
关键词：
ORGANIC ANION TRANSPORTERS; DIABETIC-NEPHROPATHY; KIDNEY-DISEASE; GENDER-DIFFERENCES; GENE; SITAGLIPTIN; FUROSEMIDE; MORTALITY; THERAPY; BINDING;
D O I：
10.1155/2015/483238
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
The aim of this study was to identify sex-dependent expression of renal transporter mRNA in lean and obese Zucker spontaneously hypertensive fatty (ZSF1) rats and to investigate the interaction of the most altered transporter, organic anion transporter 2 (Oat2), with diabetes-relevant metabolites and drugs. Higher incidence of glomerulosclerosis, tubulointerstitial fibrosis, and protein casts in Bowman's space and tubular lumen was detected by PAS staining in obese male compared to female ZSF1 rats. Real-time PCR on RNA isolated from kidney cortex revealed that Sglt1-2, Oat1-3, and Oct1 were higher expressed in kidneys of lean females. Oct2 and Mrp2 were higher expressed in obese males. Renal mRNA levels of transporters were reduced with diabetic nephropathy in females and the expression of transcription factors Hnf1 beta andHnf4 alpha in both sexes. The highest difference between lean and obese ZSF1 rats was found for Oat2. Therefore, we have tested the interaction of human OAT2 with various substances using tritium-labeled cGMP. Human OAT2 showed no interaction with diabetes-related metabolites, diabetic drugs, and ACE-inhibitors. However, OAT2-dependent uptake of cGMP was inhibited by furosemide. The strongly decreased expression of Oat2 and other transporters in female diabetic ZSF1 rats could possibly impair renal drug excretion, for example, of furosemide.
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页数：10
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