RNA-Seq analysis reveals gene expression changes induced by IL-6 trans-signaling activation in retinal endothelial cells.
RNA-Seq analysis reveals gene expression changes induced by IL-6 trans-signaling activation in retinal endothelial cells.
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RNA-Seq 分析揭示了视网膜内皮细胞中 IL-6 反式信号激活诱导的基因表达变化。
DOI：
10.1016/j.cyto.2020.155375
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发表时间：
2021-03
期刊：
影响因子：
3.8
通讯作者：
Sharma S
中科院分区：
文献类型：
--
作者：
Robinson R;Brown D;Churchwell L;Lee TJ;Kodeboyina SK;Bloom J;Sharma A;Sharma S
越来越多的证据表明，白细胞介素 6 (IL-6) 反式信号传导在糖尿病视网膜病变 (DR) 的发病机制中发挥着关键作用。我们之前已经证明，IL-6 反式信号传导的激活会诱导人视网膜内皮细胞 (HREC) 的屏障功能障碍。然而，这些效应背后的分子机制尚不清楚。本研究的目的是发现 IL-6 反式信号激活后 HREC 的整体基因表达变化。用IL-6和可溶性IL-6R处理HREC以激活IL-6反式信号传导，并使用sgp130Fc处理来抑制IL-6反式信号传导。对全局基因表达谱进行 RNA-Seq 分析。使用DESeq2确定差异表达，并进行生物信息学分析以将差异表达基因与生物学功能和通路关联起来。我们的分析揭示了 IL-6 反式信号传导激活后 HREC 中存在 445 个差异表达基因（318 个上调和 127 个下调）。我们鉴定了一些以前与 IL-6 信号传导或内皮功能障碍无关的新基因。白细胞粘附、血细胞渗出和趋化因子信号通路在差异表达基因中高度富集。用 sgp130Fc 抑制 IL-6 反式信号传导消除了这些变化，从而凸显了该药物的治疗潜力。这项研究确定了 HREC 中 IL-6 反式信号激活引起的显着基因表达变化。鉴定此类变化有可能揭示 DR 病理学中 IL-6 反式信号介导作用的精确分子机制。
Increasing evidence suggests that interleukin-6 (IL-6) trans-signaling plays a critical role in the pathogenesis of diabetic retinopathy (DR). We have previously shown that activation of IL-6 trans-signaling induces barrier dysfunction in human retinal endothelial cells (HRECs). However, the molecular mechanisms underlying these effects are not clear. The purpose of this study was to discover global gene expression changes in HRECs following activation of IL-6 trans-signaling. HRECs were treated with IL-6 and soluble IL-6R to activate IL-6 trans-signaling, and sgp130Fc treatment was used for IL-6 trans-signaling inhibition. RNA-Seq analyses were performed for global gene expression profiling. Differential expression was determined using DESeq2, and bioinformatic analyses were performed to associate the differentially expressed genes with biological functions and pathways. Our analyses revealed 445 differentially expressed genes (318 upregulated and 127 downregulated) in HRECs after IL-6 trans-signaling activation. We identified several novel genes not previously associated with IL-6 signaling or endothelial dysfunction. Leukocyte adhesion, diapedesis and chemokine signaling pathways are highly enriched in differentially expressed genes. Inhibition of IL-6 trans-signaling with sgp130Fc abrogated these changes, thus highlighting the therapeutic potential of this drug. This study identified significant gene expression changes caused by IL-6 trans-signaling activation in HRECs. Identification of such changes have the potential to uncover the precise molecular mechanisms of IL-6 trans-signaling mediated effects in the pathology of DR.
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影响因子：
7.8
作者：
Furuse, Mikio;Hata, Masaki;Furuse, Kyoko;Yoshida, Yoko;Haratake, Akinori;Sugitani, Yoshinobu;Noda, Tetsuo;Kubo, Akiharu;Tsukita, Shoichiro
通讯作者：
Tsukita, Shoichiro
DOI：
10.1007/s00417-016-3411-1
发表时间：
2017-01-01
影响因子：
2.7
作者：
Kasza, Marta;Meleg, J.;Nagy, V.
通讯作者：
Nagy, V.
影响因子：
3.7
作者：
Garcia RA;Yan M;Search D;Zhang R;Carson NL;Ryan CS;Smith-Monroy C;Zheng J;Chen J;Kong Y;Tang H;Hellings SE;Wardwell-Swanson J;Dinchuk JE;Psaltis GC;Gordon DA;Glunz PW;Gargalovic PS
通讯作者：
Gargalovic PS
影响因子：
2.1
作者：
Koskela, U. E.;Kuusisto, S. M.;Liinamaa, M. J.
通讯作者：
Liinamaa, M. J.
影响因子：
17.8
作者：
Klaassen, Ingeborg;Van Noorden, Cornelis J. F.;Schlingemann, Reinier O.
通讯作者：
Schlingemann, Reinier O.