Early growth response protein-1 upregulates long noncoding RNA Arid2-IR to promote extracellular matrix production in diabetic kidney disease
Early growth response protein-1 upregulates long noncoding RNA Arid2-IR to promote extracellular matrix production in diabetic kidney disease
复制标题
早期生长反应蛋白-1上调长非编码RNA Arid2-IR以促进糖尿病肾病细胞外基质的产生
DOI：
10.1152/ajpcell.00167.2018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Xue Yao Ming
中科院分区：
文献类型：
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作者：
Yang Yan Lin;Hu Fang;Xue Meng;Jia Yi Jie;Zheng Zong Ji;Li Yang;Xue Yao Ming
糖尿病肾病（DKD）已超过慢性肾小球肾炎成为终末期肾病的主要原因。以前，我们发现早期生长反应蛋白1（Egr 1）通过增强系膜细胞增殖和细胞外基质（ECM）的产生在DKD中起关键作用。长链非编码RNA（lncRNA）AT丰富的相互作用结构域2-IR（Arid 2-IR）已被鉴定为单侧输尿管梗阻性肾病中的十肢瘫痪同源物3（Smad 3）相关lncRNA的母体。然而，Egr 1在DKD发生发展中对Arid 2-IR的影响尚不清楚。在这项研究中，我们发现Arid 2-IR在高脂饮食和链脲佐菌素诱导的2型糖尿病小鼠和高糖培养的小鼠系膜细胞中增加，以模拟糖尿病。在小鼠系膜细胞中敲低Arid 2-IR可降低高糖诱导的胶原-α1（I）（Col 1a 1）和α-平滑肌肌动蛋白（α-SMA）的高表达水平。此外，Arid 2-IR的表达改变了Egr 1过表达引起的Col 1a 1和α-SMA的表达增加。总之，这些数据表明Arid 2-IR增加可能有助于DKD ECM的产生，Egr 1部分通过上调Arid 2-IR促进DKD ECM的产生，因此，Arid 2-IR可能是DKD治疗的新靶点。
Diabetic kidney disease (DKD) has surpassed chronic glomerulonephritis as the leading cause of end-stage renal disease. Previously, we showed that early growth response protein-1 (Egr1) plays a key role in DKD by enhancing mesangial cell proliferation and extracellular matrix (ECM) production. The long noncoding RNA (lncRNA) AT-rich interactive domain 2-IR (Arid2-IR) has been identified as a mothers against decapentaplegic homolog 3 (Smad3)-associated lncRNA in unilateral ureteral obstructive kidney disease. However, the effect of Egr1 on Arid2-IR in the development of DKD is still unknown. In this study, we found that Arid2-IR was increased in mice with high-fat diet and streptozotocin-induced type 2 diabetes and in mouse mesangial cells cultured with high glucose to mimic diabetes. Knockdown of Arid2-IR in mouse mesangial cells reduced the high expression levels of collagen-α1(I) (Col1a1) and α-smooth muscle actin (α-SMA) induced by high glucose. Furthermore, Arid2-IR expression changed the increased expression of Col1a1 and α-SMA caused by overexpression of Egr1. Overall, these data suggest that increased Arid2-IR likely contributes to ECM production in DKD and that Egr1 promotes ECM production in DKD partly by upregulating Arid2-IR. Thus, Arid2-IR may be a new target in the treatment of DKD.