miR-23a-3p regulates the inflammatory response and fibrosis in diabetic kidney disease by targeting early growth response 1.
miR-23a-3p regulates the inflammatory response and fibrosis in diabetic kidney disease by targeting early growth response 1.
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miR-23a-3p 通过靶向早期生长反应来调节糖尿病肾病的炎症反应和纤维化 1
DOI：
10.1007/s11626-021-00606-1
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Sheng S;Zou M;Yang Y;Guan M;Ren S;Wang X;Wang L;Xue Y
糖尿病肾病(DKD)已成为慢性肾脏疾病最常见的病因。蛋白尿通常被认为是肾脏损害的临床指标之一，也与DKD的进展密切相关。越来越多的证据表明，蛋白尿可诱导肾小管上皮细胞炎性细胞因子和纤维化标志物的表达上调，但其机制尚不清楚。先前，我们发现早期生长反应1(Egr1)在肾小管损伤中起关键作用。然而，Egr1在DKD发生发展中的上游机制尚不清楚。在本研究中，我们发现白蛋白刺激显著增加HK-2细胞EGR1、IL-6、肿瘤坏死因子-α和纤维连接蛋白(FN)的表达水平，而降低miR-23a-3p的表达水平。然后，我们鉴定了miR-23a-3p靶向于Egr1的3‘非翻译区，并直接抑制了Egr1的表达。此外，我们还发现，在HK-2细胞中过表达和抑制miR-23a-3p分别减弱和促进了IL-6、肿瘤坏死因子-α和FN的表达。此外，Egr1沉默逆转了miR-23a-3p抑制剂引起的炎症和纤维化。因此，我们认为miR-23a-3p通过Egr1抑制DKD的发展，提示靶向miR-23a-3p可能是治疗DKD的一种新途径。
Diabetic kidney disease (DKD) has become the most common cause of chronic kidney disease. Proteinuria is generally considered one of the clinical indicators of renal damage, and it is also closely related to the progression of DKD. Accumulating evidence indicates that proteinuria induces an upregulation of the expression levels of inflammatory cytokines and fibrosis markers in renal tubular epithelial cells, but the mechanism remains unclear. Previously, we showed that early growth response 1 (Egr1) played a key role in renal tubular injury. However, the upstream mechanism of Egr1 in the development of DKD is poorly understood. In this study, we found that albumin stimulation significantly increased the expression levels of Egr1, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and fibronectin (FN) in HK-2 cells but decreased miR-23a-3p levels. We then identified that miR-23a-3p targeted the 3′ untranslated region (UTR) of Egr1 and directly suppressed the expression of Egr1. Moreover, we found that overexpression and inhibition of miR-23a-3p in HK-2 cells attenuated and promoted the expression of IL-6, TNF-α, and FN, respectively. Additionally, Egr1 silencing reversed the inflammation and fibrosis caused by the miR-23a-3p inhibitor. Thus, we conclude that miR-23a-3p attenuates the development of DKD through Egr1, suggesting that targeting miR-23a-3p may be a novel therapeutic approach for DKD.
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作者：
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