Tain You-Lin, Hsu Chien-Ning, Chan Julie Y H, Huang Li-Tung
Departments of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Int J Mol Sci. 2015 Aug 3;16(8):17826-37. doi: 10.3390/ijms160817826.
Maternal nutrition can affect development, leading to long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether alterations in renal transcriptome are responsible for generating programmed hypertension among four different models using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received 50% caloric restriction (CR), intraperitoneal injection of 45 mg/kg streptozotocin, 60% high-fructose (HF) diet, or 1% NaCl in drinking water to conduct CR, diabetes, HF, or high-salt models, respectively. All four models induced programmed hypertension in adult male offspring. We observed 16 shared genes in a two-week-old kidney among four different models. The identified differential expressed genes (DEGs) that are related to the regulation of blood pressure included Adrb3, Alb, Apoe, Calca, Kng1, Adm2, Guca2b, Hba2, Hba-a2, and Ppara. The peroxisome proliferator-activated receptor (PPAR) signaling pathway and glutathione metabolism pathway were shared by the CR, diabetes, and HF models. Conclusively, a variety of maternal nutritional insults induced the same phenotype-programmed hypertension with differential alterations of renal transcriptome in adult male offspring. The roles of DEGs identified by the NGS in this study deserve further clarification to develop ideal maternal dietary interventions and thus spare the next generations from the burden of hypertension.
母体营养会影响发育,对后代健康产生长期影响。最常见的结果是程序性高血压。我们使用下一代RNA测序(NGS)技术,在四种不同模型中研究了肾脏转录组的改变是否是导致程序性高血压的原因。怀孕的斯普拉格-道利大鼠分别接受50%热量限制(CR)、腹腔注射45 mg/kg链脲佐菌素、60%高果糖(HF)饮食或饮用水中1%氯化钠,以建立CR、糖尿病、HF或高盐模型。所有这四种模型均在成年雄性后代中诱发了程序性高血压。我们在四种不同模型两周大的肾脏中观察到16个共享基因。鉴定出的与血压调节相关的差异表达基因(DEG)包括Adrb3、Alb、Apoe、Calca、Kng1、Adm2、Guca2b、Hba2、Hba-a2和Ppara。CR、糖尿病和HF模型共享过氧化物酶体增殖物激活受体(PPAR)信号通路和谷胱甘肽代谢通路。总之,多种母体营养损伤在成年雄性后代中诱导出相同的表型——程序性高血压,同时伴有肾脏转录组的不同改变。本研究中通过NGS鉴定出的DEG的作用值得进一步阐明,以制定理想的母体饮食干预措施,从而使后代免受高血压的负担。