Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway
Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway
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DOI：
10.1017/s2040174415007242
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发表时间：
2016-02-01
影响因子：
1.7
通讯作者：
Hu, Y.
中科院分区：
文献类型：
--
作者：
Chen, L.;Yue, J.;Hu, Y.
宫内生长受限（IUGR）与新生儿肾单位数量减少有关，从而增加患高血压的风险。我们之前的研究表明哇巴因可以保护 IUGR 期间胚胎肾脏的发育。为了探索这一分子机制，在整个怀孕期间通过限制蛋白质和热量来诱导 IUGR 大鼠，并使用微型渗透泵输送哇巴因。 RNA测序技术用于鉴定胚胎肾脏的差异表达基因（DEG）。将DEG提交至注释、可视化和综合发现数据库，并进行基因本体富集分析和京都基因和基因组百科全书（KEGG）通路分析。母亲营养不良显着降低胎儿体重，但哇巴因治疗对体重没有显着影响。在对照组和 IUGR 组之间总共检测到 322 个 DEG（177 个上调和 145 个下调）。同时，发现 IUGR 组和哇巴因治疗组之间有 318 个 DEG 存在差异表达（180 个升高，138 个降低）。 KEGG通路分析表明，母体营养不良主要破坏补体和凝血级联以及钙信号通路，哇巴因治疗可以保护这些通路。综上所述，这两种生物学途径可能在肾发生中发挥重要作用，表明针对 IUGR 不利影响的潜在新治疗靶点。
Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.