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Ageing genetic signature of hypersomatotropism
Open Biology ( IF 5.8 ) Pub Date : 2021-04-14 , DOI: 10.1098/rsob.200265
Abdalla Elbialy 1
Affiliation  

Acromegaly is a pathological condition that is caused by over-secretion of growth hormone (GH) and develops primarily from a pituitary adenoma. Excess GH exposure over a prolonged period of time leads to a wide range of systemic manifestations and comorbidities. Studying the effect of excess GH on the cellular level could help to understand the underlying causes of acromegaly health complications and comorbidities. In our previous publications, we have shown that excess GH reduces body side population (SP) stem cells and induces signs of premature ageing in an acromegaly zebrafish model. Here, we study acromegaly ageing in greater depth at the level of gene expression. We investigated whether acromegaly induces an ageing genetic signature in different organs. Using the GenAge database, our acromegaly model showed a significant enrichment of ageing genetic datasets in the muscle but not in other organs. Likewise, the hierarchical clustering of wild type (WT), acromegaly and aged RNA data from various organs revealed the similarity of gene expression profiles between the acromegaly and the aged muscles. We therefore identified overlapping differentially expressed genes (DEGs) in different organs between acromegaly and aged zebrafish. Importantly, about half of the muscle, liver and brain acromegaly DEGs overlapped with aged zebrafish DEGs. Interestingly, overlapping was observed in the same way; acromegaly-up DEGs overlapped with aged zebrafish up DEGs, not down DEGs, and vice versa. We then identified the biological functions of overlapping DEGs. Enrichment database analysis and gene ontology showed that most overlapping muscle genes were involved in ageing metabolism, while overlapping liver DEGs were involved in metabolic pathways, response to hypoxia and endoplasmic reticulum stress. Thus, this study provides a full ageing genetic signature of acromegaly at the gene expression level.



中文翻译:

生长激素过多症的衰老遗传特征

肢端肥大症是一种由生长激素 (GH) 分泌过多引起的病理状况,主要由垂体腺瘤发展而来。长时间过量接触 GH 会导致广泛的全身表现和合并症。研究过量 GH 对细胞水平的影响有助于了解肢端肥大症健康并发症和合并症的根本原因。在我们以前的出版物中,我们已经证明,过量的 GH 会减少体侧种群 (SP) 干细胞并在肢端肥大斑马鱼模型中诱导过早衰老的迹象。在这里,我们在基因表达水平上更深入地研究肢端肥大症的衰老。我们研究了肢端肥大症是否会在不同器官中诱导衰老的遗传特征。使用 GenAge 数据库,我们的肢端肥大症模型显示肌肉中老化的遗传数据集显着丰富,但在其他器官中没有。同样,来自不同器官的野生型 (WT)、肢端肥大症和老化 RNA 数据的层次聚类揭示了肢端肥大症和老化肌肉之间基因表达谱的相似性。因此,我们在肢端肥大症和老年斑马鱼的不同器官中发现了重叠的差异表达基因 (DEG)。重要的是,大约一半的肌肉、肝脏和大脑肢端肥大症 DEG 与老年斑马鱼 DEG 重叠。有趣的是,以相同的方式观察到重叠;肢端肥大症向上的 DEG 与老年斑马鱼向上的 DEG 重叠,而不是向下的 DEG,并且 肢端肥大症和来自不同器官的老化 RNA 数据揭示了肢端肥大症和老化肌肉之间基因表达谱的相似性。因此,我们在肢端肥大症和老年斑马鱼的不同器官中发现了重叠的差异表达基因 (DEG)。重要的是,大约一半的肌肉、肝脏和大脑肢端肥大症 DEG 与老年斑马鱼 DEG 重叠。有趣的是,以相同的方式观察到重叠;肢端肥大症向上的 DEG 与老年斑马鱼向上的 DEG 重叠,而不是向下的 DEG,并且 肢端肥大症和来自不同器官的老化 RNA 数据揭示了肢端肥大症和老化肌肉之间基因表达谱的相似性。因此,我们在肢端肥大症和老年斑马鱼的不同器官中发现了重叠的差异表达基因 (DEG)。重要的是,大约一半的肌肉、肝脏和大脑肢端肥大症 DEG 与老年斑马鱼 DEG 重叠。有趣的是,以相同的方式观察到重叠;肢端肥大症向上的 DEG 与老年斑马鱼向上的 DEG 重叠,而不是向下的 DEG,并且 肝脏和大脑肢端肥大症 DEGs 与老年斑马鱼 DEGs 重叠。有趣的是,以相同的方式观察到重叠;肢端肥大症向上的 DEG 与老年斑马鱼向上的 DEG 重叠,而不是向下的 DEG,并且 肝脏和大脑肢端肥大症 DEGs 与老年斑马鱼 DEGs 重叠。有趣的是,以相同的方式观察到重叠;肢端肥大症向上的 DEG 与老年斑马鱼向上的 DEG 重叠,而不是向下的 DEG,并且反之亦然。然后我们确定了重叠 DEG 的生物学功能。富集数据库分析和基因本体显示,大多数重叠的肌肉基因参与衰老代谢,而重叠的肝脏DEGs参与代谢途径、对缺氧和内质网应激的反应。因此,这项研究在基因表达水平上提供了肢端肥大症的完整衰老遗传特征。

更新日期:2021-04-14
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