MRTF-A mediated FN and ICAM-1 expression in AGEs-induced rat glomerular mesangial cells via activating STAT5
MRTF-A mediated FN and ICAM-1 expression in AGEs-induced rat glomerular mesangial cells via activating STAT5
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MRTF-A 通过激活 STAT5 介导 AGE 诱导的大鼠肾小球系膜细胞中 FN 和 ICAM-1 的表达
DOI：
10.1016/j.mce.2017.07.014
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发表时间：
2018-01-15
影响因子：
4.1
通讯作者：
Huang, Heqing
中科院分区：
文献类型：
--
作者：
Chen, Qiuhong;Huang, Junying;Huang, Heqing
晚期糖基化终末产物 (AGE) 在糖尿病下加速形成，在糖尿病肾病 (DN) 系膜区域的炎症和纤维化中发挥作用。然而，介导细胞对 AGEs 反应的转录调节剂仍然很模糊。我们的目标是确定心肌素相关转录因子 (MRTF)-A（参与平滑肌细胞表型转录调节的关键蛋白）是否与 AGE 造成的肾小球系膜细胞 (GMC) 损伤有关，如果是，那么 MRTF-A 如何促进 AGE 引发的系膜功能障碍。在本研究中，MRTF-A 在大鼠 GMC 中的蛋白表达和核转位方面被 AGE 激活。 MRTF-A 过表达协同增强 AGEs 对 FN 和 ICAM-1 的诱导。反过来，MRTF-A 的消耗消除了 AGE 引发的致病程序。然后，通过干扰MRTF-A，观察到STAT1、STAT3和STAT5核转位，并筛选出STAT5，当MRTF-A耗尽时，STAT5明显减少。进一步研究表明MRTF-A与STAT5相互作用并促进其核积累和转录活性。因此，我们目前的研究结果表明MRTF-A在AGEs诱导的GMCs损伤中发挥作用，并进一步揭示其潜在的分子机制与激活核因子STAT5有关。 (C) 2017 Elsevier B.V. 保留所有权利。
Advanced glycation end products (AGEs), formed at an accelerated rate under diabetes, play a role in inflammation and fibrosis in mesangial areas in diabetic nephropathy (DN). However, the transcriptional modulator that mediates the cellular response to AGEs remains largely obscure. Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, was responsible for the glomerular mesangial cells (GMCs) injury by AGEs, and, if so, how MRTF-A promoted mesangial dysfunction initiated by AGEs. In this study, MRTF-A was activated by AGEs in terms of protein expression and nuclear translocation in rat GMCs. MRTF-A overexpression synergistically enhanced the induction of FN and ICAM-1 by AGEs. In contract, depletion of MRTF-A abrogated the pathogenic program triggered by AGEs. Then, by interfering with MRTF-A, STAT1, STAT3 and STAT5 nuclear translocation were observed and we screened out STAT5, which was decreased obviously when MRTF-A depleted. Further investigation showed that MRTF-A interacted with STAT5 and promoted its nuclear accumulation and transcriptional activity. Therefore, our present findings suggested a role of MRTF-A in AGEs-induced GMCs injury, and further revealed that the underlying molecular mechanism was related to activating the nuclear factor STAT5. (C) 2017 Elsevier B.V. All rights reserved.