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首页> 外文期刊>American Journal of Physiology >Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule.
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Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule.

机译：肝X受体激动剂TO-901317上调肾近端直小管中SCD1的表达。

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摘要

Liver X receptors (LXRs), including LXRalpha and LXRbeta, are intracellular sterol sensors that regulate expression of genes controlling fatty acid and cholesterol absorption, excretion, catabolism, and cellular efflux. Because the kidney plays an important role in lipid metabolism and dyslipidemia accelerates renal damage, we investigated the effect of TO-901317, an LXR agonist, on the gene expression profile in mouse kidney. Treatment of C57 Bl/6 mice with TO-901317 (3 mg.kg(-1).day(-1)) for 3 days resulted in 51 transcripts that were significantly regulated in the kidney. Among them, the stearoyl-CoA desaturase-1 (SCD1) was upregulated most dramatically. Northern blot analysis revealed that SCD1 mRNA levels were markedly higher than that in control kidneys. Enhanced SCD1 expression by TO-901317 also resulted in increased fatty acid desaturation in the kidney. In control mice, constitutive renal SCD1 expression was low; however, TO-901317 treatment markedly increased SCD1 expression in the outer stripe of the outer medulla as assessed by both in situ hybridization and immunostain. Double-labeling studies further indicated that SCD1 mRNA was selectively expressed in proximal straight tubules negative for aquaporin-2 and Tamm-Horsfall protein. In vitro studies in cultured murine proximal tubule cells further demonstrated that LXR activation enhanced SCD1 transcription via increased sterol regulatory element binding protein-1. Taken together, these data suggest LXR activation of SCD1 expression may play an important role in regulating lipid metabolism and cell function in renal proximal straight tubules.
机译：肝X受体（LXR），包括LXRalpha和LXRbeta，是细胞内固醇传感器，可调节控制脂肪酸和胆固醇吸收，排泄，分解代谢和细胞外排的基因的表达。由于肾脏在脂质代谢中起重要作用，血脂异常会加速肾脏损害，因此我们研究了LXR激动剂TO-901317对小鼠肾脏基因表达谱的影响。用TO-901317（3 mg.kg（-1）.day（-1））对C57 Bl / 6小鼠进行3天的治疗，导致51个转录本在肾脏中得到显着调节。其中，硬脂酰辅酶A去饱和酶-1（SCD1）被最显着上调。 Northern印迹分析显示，SCD1 mRNA水平显着高于对照肾脏。 TO-901317增强的SCD1表达也导致肾脏中脂肪酸去饱和增加。在对照小鼠中，组成型肾SCD1表达低;然而，通过原位杂交和免疫染色评估，TO-901317处理显着增加了延髓外条纹中SCD1的表达。双重标记研究进一步表明，SCD1 mRNA在水通道蛋白2和Tamm-Horsfall蛋白阴性的近端直小管中选择性表达。在培养的鼠近端肾小管细胞中的体外研究进一步表明，LXR激活通过增加固醇调节元件结合蛋白-1来增强SCD1转录。综上所述，这些数据表明LXR激活SCD1表达可能在调节肾近端直小管的脂质代谢和细胞功能中起重要作用。

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