The effect of lncRNA-ARAP1-AS2/ARAP1 on high glucose-induced cytoskeleton rearrangement and epithelial-mesenchymal transition in human renal tubular epithelial cells
The effect of lncRNA-ARAP1-AS2/ARAP1 on high glucose-induced cytoskeleton rearrangement and epithelial-mesenchymal transition in human renal tubular epithelial cells
复制标题
lncRNA—ARAP1—AS2/ARAP1对高糖诱导的人肾小管上皮细胞细胞骨架重排和上皮—间质转化的影响
DOI：
10.1002/jcp.29512
复制
发表时间：
2020-01-24
影响因子：
5.6
通讯作者：
Fan, Qiuling
中科院分区：
文献类型：
--
作者：
Li, Lulu;Xu, Li;Fan, Qiuling
上皮-间质转化（EMT）在糖尿病肾纤维化中起重要作用。ARAP1基因位于2型糖尿病的危险等位基因附近，其功能与细胞骨架重排、高尔基体重塑和膜受体的内噬运输有关。ARAP1及其反义RNA ARAP1- as2在糖尿病发病中的作用尚不清楚。为了阐明ARAP1及其反义RNA在糖尿病及其相关并发症中的作用，我们检测了这些转录物在高糖（HG）条件下的表达是否发生变化。为此，我们检测了HK-2细胞中的转录物水平，并探讨了ARAP1和ARAP1- as2在HK-2细胞EMT过程中的作用。我们发现HG条件下HK-2细胞中ARAP1- as2和ARAP1的表达增加，并观察到ARAP1- as2的过表达显著增加了EMT过程。此外，HG上调了HK-2细胞中的Cdc42-GTP水平，增加了细胞骨架重排、细胞活力和迁移。敲除ARAP1后，Cdc42-GTP水平降低；细胞骨架重组、细胞活力和迁移过程减少；EMT和纤维化标志蛋白的表达。总之，我们的研究结果表明，ARAP1- as2 /ARAP1可能通过增加Cdc42-GTP水平参与HK-2细胞的细胞骨架重排和EMT过程。
The epithelial-mesenchymal transition (EMT) plays an important role in diabetic renal fibrosis. The ARAP1 gene is located near risk alleles for Type 2 diabetes, and its function has been linked to cytoskeleton rearrangement, Golgi apparatus remodeling, and endocytic trafficking of membrane receptors. The role of ARAP1 and its antisense RNA, ARAP1-AS2, in the pathogenesis of diabetes is unclear. To clarify the roles of ARAP1 and its antisense RNA in diabetes and related complications, we examined if the expression of these transcripts changed under high glucose (HG) conditions. To do this, we examined transcript levels in HK-2 cells, and explored the roles of ARAP1 and ARAP1-AS2 in the EMT process in HK-2 cells. We found increased expression of ARAP1-AS2 and ARAP1 in HK-2 cells under HG condition, and observed that the overexpression of ARAP1-AS2 significantly increased the EMT process. In addition, HG upregulated Cdc42-GTP levels in HK-2 cells, and increased cytoskeleton rearrangement, cell viability, and migration. After knockdown of ARAP1, the level of Cdc42-GTP was decreased; cytoskeleton reorganization, cell viability, and migration processes were decreased; and EMT and expression of fibrosis marker protein. Overall, our results indicated that ARAP1-AS2/ARAP1 may participate in cytoskeleton rearrangement and EMT processes in HK-2 cells through increased Cdc42-GTP levels.