Expression profiling of small, noncoding RNAs in physiologically hypertrophied rat hearts. Rattus norvegicus

Purpose: Different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy but their role during physiological hypertrophy is largely unexplored. Hence, this study is aimed at revealing the global expression profile of miRNAs during physiological cardiac hypertrophy. Methods: Chronic swimming protocol continuously for eight weeks resulted in induction of physiological hypertrophy in rats and histopathology revealed the absence of tissue damage, apoptosis or fibrosis. Subsequently, the total RNA was isolated and small RNA sequencing was executed in Illumina HiSeq 2000. Results: Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during physiological hypertrophy. The expression profile of the significantly differentially expressed miRNAs were validated by qPCR. Conclusions: This is the first report to reveal the involvement of a large number of apoptotic miRNAs during physiological cardiac hypertrophy including the previously unknown cardiac players like miR-99, miR-100, miR-191, miR-181 and miR-19. Our data indicates that regulation of these apoptotic miRNAs can be one of the major key factor in determining pathological or physiological hypertrophy by controlling apoptosis, fibrosis and cell death mechanisms. Overall design: Heart small RNA profiles of 16-week old control and physiologically hypertrophied wistar rat were generated by deep sequencing using Illumina HiSeq 2000

研究背景：多项研究已证实微小核糖核酸（microRNAs, miRNAs）在病理性心肌肥厚中的重要作用，但这类分子在生理性心肌肥厚中的功能尚未得到充分探索。因此本研究旨在揭示生理性心肌肥厚过程中微小核糖核酸的全局表达谱。
实验方法：连续8周的慢性游泳造模方案成功诱导大鼠产生生理性心肌肥厚；组织病理学检测结果显示，造模后未出现组织损伤、细胞凋亡或纤维化现象。随后提取总RNA，使用Illumina HiSeq 2000平台开展小RNA测序。
实验结果：小RNA测序读段分析显示，生理性心肌肥厚过程中存在大量微小核糖核酸的差异表达；通过qPCR验证了显著差异表达的微小核糖核酸的表达谱。
研究结论：本研究首次报道了大量凋亡相关微小核糖核酸参与生理性心肌肥厚过程，其中包括此前尚未明确的心肌调控分子如miR-99、miR-100、miR-191、miR-181及miR-19。本研究数据表明，调控此类凋亡相关微小核糖核酸，可通过影响细胞凋亡、纤维化及细胞死亡机制，成为决定心肌肥厚为病理性或生理性的关键调控因素之一。
整体实验设计：采用Illumina HiSeq 2000平台进行深度测序，获取16周龄正常对照及生理性肥厚的Wistar大鼠的心脏小RNA表达谱。