TGFβ and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activation.
TGFβ and CCN2/CTGF mediate actin related gene expression by differential E2F1/CREB activation.
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DOI：
10.1186/1471-2164-14-525
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发表时间：
2013-08-01
期刊：
影响因子：
4.4
通讯作者：
Crean J
中科院分区：
文献类型：
--
作者：
Faherty N;O'Donovan H;Kavanagh D;Madden S;McKay GJ;Maxwell AP;Martin F;Godson C;Crean J
CCN2/CTGF是糖尿病肾病转化生长因子β驱动反应的效应分子。我们已经确定CCN2和转化生长因子β之间的相互作用导致表型分化改变并抑制细胞迁移。在这里，我们确定了与这种表型相关的基因表达谱，并定义了差异肌动蛋白相关基因表达和细胞骨架功能的转录基础。从一组由转化生长因子β和ccn2调控的基因中，我们使用共惯性分析来识别并实验验证转录因子E2F1和CREB的子集，它们调控与肌动蛋白动态变化和细胞肥大有关的表达指纹。重要的是，肌动蛋白相关基因包含E2F1和CREB结合位点，根据数据集中的表达谱分层。对糖尿病肾病患者的肌动蛋白和细胞骨架相关基因的进一步分析表明，在肾脏疾病的发展过程中，这一程序重复了。Rho家族成员CDC42也被发现在转化生长因子β和CCN2处理的细胞中唯一被激活；CDC42相互作用的基因在糖尿病肾病中有不同的调节。转化生长因子β和CCN2减弱CREB，增强E2F1转录激活，可能通过改变肌动蛋白、细胞骨架和细胞生长/肥大基因活性而影响糖尿病肾病的细胞功能障碍。细胞骨架调节因子CDC42可能在这一信号反应中发挥作用。
CCN2/CTGF is an established effector of TGFβ driven responses in diabetic nephropathy. We have identified an interaction between CCN2 and TGFβ leading to altered phenotypic differentiation and inhibited cellular migration. Here we determine the gene expression profile associated with this phenotype and define a transcriptional basis for differential actin related gene expression and cytoskeletal function. From a panel of genes regulated by TGFβ and CCN2, we used co-inertia analysis to identify and then experimentally verify a subset of transcription factors, E2F1 and CREB, that regulate an expression fingerprint implicated in altered actin dynamics and cell hypertrophy. Importantly, actin related genes containing E2F1 and CREB binding sites, stratified by expression profile within the dataset. Further analysis of actin and cytoskeletal related genes from patients with diabetic nephropathy suggests recapitulation of this programme during the development of renal disease. The Rho family member Cdc42 was also found uniquely to be activated in cells treated with TGFβ and CCN2; Cdc42 interacting genes were differentially regulated in diabetic nephropathy. TGFβ and CCN2 attenuate CREB and augment E2F1 transcriptional activation with the likely effect of altering actin cytoskeletal and cell growth/hypertrophic gene activity with implications for cell dysfunction in diabetic kidney disease. The cytoskeletal regulator Cdc42 may play a role in this signalling response.
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影响因子：
7.5
作者：
Delon, Isabelle;Brown, Nicholas H.
通讯作者：
Brown, Nicholas H.
影响因子：
5.3
作者：
Itoh, RE;Kurokawa, K;Matsuda, M
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影响因子：
4.8
作者：
Crean, JKG;Finlay, D;Brady, HR
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DOI：
10.1073/pnas.97.8.4017
发表时间：
2000-04-11
影响因子：
11.1
作者：
Gallagher, AR;Cedzich, A;Witzgall, R
通讯作者：
Witzgall, R
影响因子：
13.6
作者：
Riser, BL;Denichilo, M;Narins, RG
通讯作者：
Narins, RG