Inhibition of microRNA‐182‐5p contributes to attenuation of lupus nephritis via Foxo1 signaling
Inhibition of microRNA‐182‐5p contributes to attenuation of lupus nephritis via Foxo1 signaling
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DOI：
10.1016/j.yexcr.2018.09.026
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发表时间：
2018-12
影响因子：
3.7
通讯作者：
Xiaoyang Wang;Guangjie Wang;Xiaoxue Zhang;Y. Dou;Yijun Dong;Dong Liu;Jing Xiao;Zhanzheng Zhao
中科院分区：
文献类型：
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作者：
Xiaoyang Wang;Guangjie Wang;Xiaoxue Zhang;Y. Dou;Yijun Dong;Dong Liu;Jing Xiao;Zhanzheng Zhao
MIR-182-5P抑制Foxo1的表达，Foxo1是肾脏疾病的保护因子，在系统性红斑狼疮患者中上调。因此，我们推测miR-182-5p/Foxo1轴功能异常参与了狼疮性肾炎(LN)的发生发展。首先，我们研究了miR-182-5p和Foxo1在LN患者和LN MRL/LPR小鼠生长发育过程中的表达。然后，我们给mrl/lpr小鼠注射miR-182-5p，观察抑制miR-182-5p对肾脏结构和功能的影响。体外，我们用转化生长因子-β1作用于肾细胞系，探讨肾纤维化与miR-182-5p的关系。高时辰指数患者miR-182-5p表达上调，Foxo1表达受抑制。小鼠LN的进展与miR-182-5p水平升高和Foxo1水平下降有关。抑制miR-182-5p可改善LN相关的肾脏结构和功能损害，并增加Foxo1的表达。体外给予转化生长因子-β-1可增加肾细胞miR-182-5p的表达，并呈剂量依赖性。目前的研究表明，在LN患者中miR-182-5p的表达增加，参与了Foxo1的抑制和LN的发生发展。
MiR-182–5p suppresses expression of Foxo1 that is a protective factor in renal disorders and is up-regulated in systemic lupus erythematosus patients. Thus, we hypothesized that dys-function of miR-182–5p/Foxo1 axis contributed to development of lupus nephritis (LN). Firstly, we investigated the expressions of miR-182–5p and Foxo1 in LN patients and during growth of LN MRL/lpr mice. Then we subjected MRL/lpr mice to the injection of miR-182–5p antagomirs and assessed the effect of miR-182–5p inhibition on renal structure and function.In vitro, we administrated renal cell lines with TGF-β1 to explore the relation between renal fibrosis and miR-182–5p. The level of miR-182–5p was up-regulated in high Chronicity Index patients while the level of Foxo1 was suppressed. The progression of LN in mice was associated with the increased level of miR-182–5p and the decreased level of Foxo1. The inhibition of miR-182–5p ameliorated renal structure and function impairments associated with LN, along with the increased expression of Foxo1. The administration of TGF-β1 in vitro increased the expression of miR-182–5p in renal cells in an overall dose-dependent manner. The current study demonstrated that the expression of miR-182–5p was increased in LN patients, contributing to the suppression of Foxo1 and development of LN.