The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells.
The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells.
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DOI：
10.1038/ki.2012.393
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发表时间：
2013-05
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
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甲基巴多索龙是一种合成三萜类化合物，可改善慢性肾病和2型糖尿病患者的估计肾小球滤过率（GFR）。由于系膜细胞的收缩活性可能影响肾小球滤过，我们评估了与甲基巴多索龙结构相似的合成三萜类化合物RTA 405对大鼠GFR和新鲜分离的肾小球中系膜细胞收缩性的影响。在大鼠中，RTA 405增加基础GFR，通过菊粉清除率评估，并减弱血管紧张素II诱导的GFR下降。RTA 405增加了滤过分数，但不影响动脉血压或肾血浆流量。来自RTA 405处理的大鼠的肾小球对血管紧张素II诱导的离体体积减小具有抗性。在培养的系膜细胞中，RTA 405以剂量和时间依赖性方式减弱血管紧张素II刺激的收缩。此外，肾小球系膜细胞中Nrf2靶向基因转录（调节抗氧化、抗炎和细胞保护反应）与基础水平降低和血管紧张素II刺激的过氧化氢和钙离子水平降低相关。这些机制有助于在大鼠中用RTA 405治疗后发生的GFR增加，并且可能是甲基巴多索龙对患者中估计的GFR的影响的基础。
Bardoxolone methyl, a synthetic triterpenoid, improves the estimated glomerular filtration rate (GFR) in patients with chornic kidney disease and type 2 diabetes. Since the contractile activity of mesangial cells may influence glomerular filtration, we evaluated the effect of the synthetic triterpenoid RTA405 with structural similarity to bardoxolone methyl, on GFR in rats and on mesangial cell contractility in freshly isolated glomeruli. In rats, RTA 405 increased basal GFR, assessed by inulin clearance, and attenuated the angiotensin II-induced decline in GFR. RTA 405 increased the filtration fraction, but did not affect arterial blood pressure or renal plasma flow. Glomeruli from RTA 405-treated rats were resistant to angiotensin II-induced volume reduction ex vivo. In cultured mesangial cells, angiotensin II-stimulated contraction was attenuated by RTA 405, in a dose- and time-dependent fashion. Further, Nrf2 targeted gene transcription (regulates antioxidant, anti-inflammatory, and cytoprotective responses) in mesangial cells was associated with decreased basal and reduced angiotensin II-stimulated hydrogen peroxide and calcium ion levels. These mechanisms contribute to the GFR increase that occurs following treatment with RTA 405 in rats and may underlie the effect of bardoxolone methyl on the estimated GFR in patients.
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影响因子：
5.5
作者：
Graham, Sarabeth;Gorin, Yves;Ma, Rong
通讯作者：
Ma, Rong
影响因子：
4.8
作者：
Gorin, Y;Block, K;Abboud, HE
通讯作者：
Abboud, HE
DOI：
10.1073/pnas.0500815102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Liby, KT;Talalay, P
通讯作者：
Talalay, P
影响因子：
13.2
作者：
Levin, Adeera;Djurdjev, Ognjenka;Er, Lee
通讯作者：
Er, Lee
影响因子：
7.7
作者：
Jiang T;Huang Z;Lin Y;Zhang Z;Fang D;Zhang DD
通讯作者：
Zhang DD