Effect of simvastatin on high glucose- and angiotensin II-induced activation of the JAK/STAT pathway in mesangial cells
Effect of simvastatin on high glucose- and angiotensin II-induced activation of the JAK/STAT pathway in mesangial cells
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DOI：
10.1152/ajprenal.00502.2005
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发表时间：
2006-07-01
影响因子：
4.2
通讯作者：
Marrero, Mario B.
中科院分区：
文献类型：
--
作者：
Banes-Berceli, Amy K.;Shaw, Sean;Marrero, Mario B.
辛伐他汀对高糖和血管紧张素II诱导的系膜细胞JAK/STAT通路激活的影响美国肾脏生理学杂志291：F116-F121，2006年。首次发表于2006年1月31日; doi：10.1152/ajprenal.00502.2005。在本研究中，我们研究了辛伐他汀对高糖（HG）和ANG II激活JAK 2-STAT信号级联反应和诱导肾小球系膜细胞（GMC）生长的能力的影响。我们发现辛伐他汀预处理显著抑制HG和ANG II诱导的GMC中IV型胶原的产生、JAK 2的激活以及STAT 1和STAT 3的磷酸化。我们还发现HG和ANG II对JAK 2的激活依赖于Rho家族的GTP酶。与这些体外结果一致，在链脲佐菌素诱导的HG糖尿病大鼠模型中，通过给予辛伐他汀，肾小球中的白蛋白排泄和JAK 2、STAT 1和STAT 3磷酸化均减弱。这项研究表明，辛伐他汀阻断血管紧张素II诱导的JAK/STAT通路在糖尿病环境中，在体外和体内的激活，从而提供了新的见解，早期糖尿病肾病的分子机制。
Effect of simvastatin on high glucose- and angiotensin II-induced activation of the JAK/STAT pathway in mesangial cells. Am J Physiol Renal Physiol 291: F116-F121, 2006. First published January 31, 2006; doi:10.1152/ajprenal.00502.2005.-In the current study, we investigated the effect of simvastatin on the ability of high glucose (HG) and ANG II to activate the JAK2-STAT signaling cascade and induce glomerular mesangial cell (GMC) growth. We found that pretreatment with simvastatin significantly inhibited HG- and ANG II-induced collagen IV production, JAK2 activation, and phosphorylation of STAT1 and STAT3 in GMC. We also found that the activation of JAK2 by HG and ANG II was dependent on the Rho family of GTPases. Consistent with these in vitro results, both albumin protein excretion and phosphorylation of JAK2, STAT1, and STAT3 were attenuated in renal glomeruli by administration of simvastatin in a streptozotocin-induced rat model of HG diabetes. This study demonstrates that simvastatin blocks ANG II-induced activation of the JAK/STAT pathway in the diabetic environment, in vitro and in vivo, and, thereby, provides new insights into the molecular mechanisms underlying early diabetic nephropathy.