Alpha-lipoic acid ameliorates the epithelial mesenchymal transition induced by unilateral ureteral obstruction in mice.
Alpha-lipoic acid ameliorates the epithelial mesenchymal transition induced by unilateral ureteral obstruction in mice.
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DOI：
10.1038/srep46065
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发表时间：
2017-04-05
影响因子：
4.6
通讯作者：
Park DJ
中科院分区：
文献类型：
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作者：
Cho HS;Kim JH;Jang HN;Lee TW;Jung MH;Kim TH;Chang SH;Park DJ
上皮间质转化（epithelial-to-mesenchymal transition， EMT）是肾间质纤维化的机制之一。了解肾纤维化的EMT对肾脏疾病患者具有重要的治疗意义。α -硫辛酸（ALA）是一种具有抗氧化特性的天然化合物。ALA在急性肾损伤伴肾小管凋亡、肾炎症和氧化应激中进行了研究。我们研究了ALA对emt介导的单侧输尿管梗阻小鼠肾间质纤维化的影响。UUO小鼠出现严重的小管萎缩和小管间质纤维化，术后7天后出现强烈的EMT反应和ECM沉积。相比之下，ala处理的UUO小鼠仅表现出中度损伤和最小的纤维化，ECM蛋白、炎症因子和EMT标记物的表达也有较大的降低。ALA被证明参与抑制与EMT相关的浸润性巨噬细胞和间质纤维化的进展。它还通过降低基质金属蛋白酶的表达，减轻了管状基底膜的破坏。这是第一个在UUO小鼠模型中显示ALA调节EMT的研究。我们的研究结果表明，ALA作为一种预防和治疗慢性肾脏疾病的药物值得进一步探索。
The epithelial-to-mesenchymal transition (EMT) is one of mechanisms that induce renal interstitial fibrosis. Understanding EMT in renal fibrosis has important therapeutic implications for patients with kidney disease. Alpha-lipoic acid (ALA) is a natural compound with antioxidant properties. Studies for ALA are performed in acute kidney injury with renal tubular apoptosis, renal inflammation, and oxidative stress. We investigated the effects of ALA on EMT-mediated renal interstitial fibrosis in mice with unilateral ureteral obstruction (UUO). UUO mice developed severe tubular atrophy and tubulointerstitial fibrosis, with a robust EMT response and ECM deposition after 7 postoperative days. In contrast, ALA-treated UUO mice showed only moderate injury and minimal fibrosis and also larger reductions in the expression of ECM proteins, inflammatory factors, and EMT markers. ALA was shown to be involved in the suppression of infiltrating macrophages associated with EMT and the progression of interstitial fibrosis. It also lessened the destruction of the tubular basement membrane, by reducing the expression of matrix metalloproteinases. This is the first study to show that ALA modulates EMT in a UUO mouse model. Our results suggest that ALA merits further exploration as a therapeutic agent in the prevention and treatment of chronic kidney disease.