Deep transcriptomic profiling of Dahl salt-sensitive rat kidneys with mutant form of Resp18.
Deep transcriptomic profiling of Dahl salt-sensitive rat kidneys with mutant form of Resp18.
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DOI：
10.1016/j.bbrc.2021.07.071
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发表时间：
2021-10-01
影响因子：
3.1
通讯作者：
Kumarasamy S
中科院分区：
文献类型：
--
作者：
Ashraf UM;Mell B;Jose PA;Kumarasamy S
调节内分泌特异性蛋白 18 (Resp18) 的表达位于多种组织和细胞类型中；然而，其确切的细胞功能尚不清楚。我们之前表明，与 SS 大鼠相比，对 Dahl SS (SS) 大鼠（Resp18 突变体）中的 Resp18 位点进行靶向破坏会导致血压 (BP) 升高、肾纤维化增加、尿蛋白排泄增加，并且与 SS 大鼠相比，长期（6 周）2% 高盐 (HS) 饮食后平均生存时间缩短。基于这种显着的肾损伤表型，我们假设在 SS 大鼠中靶向破坏 Resp18 通过改变肾转录组响应 HS 的特征来促进早发高血压信号事件。为了检验这一假设，SS 和 Resp18 突变大鼠均接受为期 7 天的 2% HS 饮食，并通过无线电遥测技术记录血压。在接受 HS 饮食 7 天后，在整个昼夜周期中，与 SS 大鼠相比，Resp18 突变体大鼠的收缩压显着升高。因此，我们试图研究 Resp18 突变大鼠对 HS 的肾脏转录组反应。通过 RNA 测序，Resp18 突变大鼠表现出 25 个肾脏基因的差异表达，包括 Ren 的上调。通过 qRT-PCR 证实了肾 Ren 和其他差异表达基因的上调。此外，在 HS 治疗 7 天后，与 WT SS 大鼠相比，Resp18 突变体大鼠的循环肾素活性显着更高。总的来说，这些观察结果表明，SS 大鼠中 Resp18 基因的破坏与肾脏转录组学特征的改变有关，这是对盐负荷的早期反应。
Expression of Regulated endocrine specific protein 18 (Resp18) is localized in numerous tissues and cell types; however, its exact cellular function is unknown. We previously showed that targeted disruption of the Resp18 locus in the Dahl SS (SS) rat (Resp18mutant) results in higher blood pressure (BP), increased renal fibrosis, increased urinary protein excretion, and decreased mean survival time following a chronic (6 weeks) 2% high salt (HS) diet compared with the SS rat. Based on this prominent renal injury phenotype, we hypothesized that targeted disruption of Resp18 in the SS rat promotes an early onset hypertensive-signaling event through altered signatures of the renal transcriptome in response to HS. To test this hypothesis, both SS and Resp18mutant rats were exposed to a 7-day 2% HS diet and BP was recorded by radiotelemetry. After a 7-day exposure to the HS diet, systolic BP was significantly increased in the Resp18mutant rat compared with the SS rat throughout the circadian cycle. Therefore, we sought to investigate the renal transcriptomic response to HS in the Resp18mutant rat. Using RNA sequencing, Resp18mutant rats showed a differential expression of 25 renal genes, including upregulation of Ren. Upregulation of renal Ren and other differentially expressed genes were confirmed via qRT-PCR. Moreover, circulating renin activity was significantly higher in the Resp18mutant rat compared with the WT SS rat after 7 days on HS. Collectively, these observations demonstrate that disruption of the Resp18 gene in the SS rat is associated with an altered renal transcriptomics signature as an early response to salt load.
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影响因子：
4.6
作者：
Dunbar DR;Khaled H;Evans LC;Al-Dujaili EA;Mullins LJ;Mullins JJ;Kenyon CJ;Bailey MA
通讯作者：
Bailey MA
影响因子：
5.6
作者：
Muñoz-Durango N;Fuentes CA;Castillo AE;González-Gómez LM;Vecchiola A;Fardella CE;Kalergis AM
通讯作者：
Kalergis AM
影响因子：
30.8
作者：
Le Goff, Carine;Morice-Picard, Fanny;Dagoneau, Nathalie;Wang, Lauren W.;Perrot, Claire;Crow, Yanick J.;Bauer, Florence;Flori, Elisabeth;Prost-Squarcioni, Catherine;Krakow, Deborah;Ge, Gaoxiang;Greenspan, Daniel S.;Bonnet, Damien;Le Merrer, Martine;Munnich, Arnold;Apte, Suneel S.;Cormier-Daire, Valerie
通讯作者：
Cormier-Daire, Valerie
影响因子：
5.6
作者：
Culver S;Li C;Siragy HM
通讯作者：
Siragy HM
影响因子：
4.6
作者：
Kumarasamy, Sivarajan;Waghulde, Harshal;Joe, Bina
通讯作者：
Joe, Bina