Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.
Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.
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小檗碱通过抑制实验性糖尿病肾病模型中的 S1P-S1P2 受体途径来降低纤连蛋白表达
DOI：
10.1371/journal.pone.0043874
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Huang K;Liu W;Lan T;Xie X;Peng J;Huang J;Wang S;Shen X;Liu P;Huang H
肾小球细胞外基质（ECM）的积聚是糖尿病肾纤维化的重要病理特征之一。纤维连接蛋白（FN）是ECM的重要组成部分。我们的前期研究表明，鞘氨醇激酶1（SphK 1）-鞘氨醇1-磷酸（S1 P）信号通路的激活在糖尿病状态下肾小球系膜细胞（GMCs）FN的产生中起着关键的调节作用。在5种S1 P受体中，S1 P2受体的激活最为丰富。小檗碱（BBR）治疗还有效抑制糖尿病模型肾脏中SphK 1活性和S1 P产生，从而改善肾损伤。基于这些数据，我们进一步探讨了BBR是否可以通过S1 P2受体阻止糖尿病条件下GMCs中FN的产生。在这里，我们发现，BBR显着下调S1 P2受体在糖尿病大鼠肾脏和GMC暴露于高糖（HG）的表达，同时抑制S1 P2受体介导的FN过度生产。BBR还能明显抑制HG诱导的NF-κB的活化，并伴有S1 P2受体和FN表达的降低。综上所述，我们的研究结果表明，BBR通过作用于糖尿病条件下系膜中的S1 P2受体来降低FN表达。BBR在S1 P2受体表达调控中的作用可能与其抑制NF-κB活化密切相关。
The accumulation of glomerular extracellular matrix (ECM) is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN) is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1)-sphingosine 1- phosphate (S1P) signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs) under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR) treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG) and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.
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影响因子：
3.9
作者：
Lan, Tian;Shen, Xiaoyan;Huang, Heqing
通讯作者：
Huang, Heqing
影响因子：
4.1
作者：
Jiang, Qin;Liu, Peiqing;Huang, Heqing
通讯作者：
Huang, Heqing
影响因子：
4.1
作者：
Wahab, Nadia;Cox, Dimity;Mason, Roger M.
通讯作者：
Mason, Roger M.
影响因子：
--
作者：
Imasawa, Toshiyuki;Kitamura, Hiroshi;Yatomi, Yutaka
通讯作者：
Yatomi, Yutaka
影响因子：
4
作者：
Amasheh, Maren;Fromm, Anja;Schulzke, Joerg-Dieter
通讯作者：
Schulzke, Joerg-Dieter