RNA-Seq analysis reveals critical transcriptome changes caused by sodium butyrate in DN mouse models.
RNA-Seq analysis reveals critical transcriptome changes caused by sodium butyrate in DN mouse models.
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DOI：
10.1042/bsr20203005
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发表时间：
2021-04-30
影响因子：
4
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Yang H;Zhang Z;Peng R;Zhang L;Liu H;Wang X;Tian Y;Sun Y
糖尿病肾病是糖尿病的常见并发症，是终末期肾病的主要原因。丁酸钠(NAB)是一种短链脂肪酸(SCFA)，是肠道细菌的代谢产物，其对肾脏的保护作用已有报道。然而，其潜在机制仍不清楚。本研究旨在探讨NAB对糖尿病肾病大鼠全球转录组改变的影响。本研究将8周龄糖尿病肾病雄性db/db小鼠随机分为两组：糖尿病肾病+NAB组(5g/kg/d)和糖尿病肾病组(生理盐水治疗)。另取正常db/m小鼠作为正常对照组。测定三组小鼠的血糖、体重、尿微量白蛋白和尿肌酐。通过RNA测序(RNA-Seq)进行全转录组分析，以评估长非编码RNA(LncRNAs)和信使RNAs(MRNAs)的图谱。生物信息学分析预测糖尿病肾病中潜在的NAB相关的lncRNAs和基因。用实时定量聚合酶链式反应(qRT-PCRS)检测NAB处理后肾组织和系膜细胞中lncRNAs和mRNAs的表达。本研究结果表明，NAB可改善糖尿病肾病小鼠的肾功能障碍。此外，RNA-Seq结果表明，与糖尿病肾病组相比，糖尿病肾病+NAB组的一些lncRNAs和mRNAs发生了逆转改变。此外，NAB相关LncRNAs的整合共表达网络显示这些LncRNAs与155个关键的mRNAs相互作用。此外，炎症相关的lncRNAs和mRNAs的共表达网络表明，那些被逆转的lncRNAs和mRNAs也在炎症反应中发挥重要作用。综上所述，本研究提示NAB可改善糖尿病所致的肾功能障碍，并调节糖尿病肾病的转录组变化。
Diabetic nephropathy (DN)—a common complication of diabetes—is the primary cause of end-stage renal disease. Sodium butyrate (NaB) is a short-chain fatty acid (SCFA) that is a metabolic product of intestinal bacterium, and its protective effect on the kidney has been reported in cases of DN. However, its underlying mechanism remains unclear. The aim of the present study was to investigate the effect of NaB on globe transcriptome changes in DN. In our study, 8-week-old male db/db mice suffering from DN were randomly divided into two groups: the DN+NaB group (DN mice treated with NaB, 5 g/kg/day) and the DN group (DN mice treated with saline). Further, normal db/m mice were used as the normal control (NC) group. The blood glucose, body weight, urinary microalbumin and urinary creatinine of mice were measured for all three groups. Whole-transcriptome analysis was performed by RNA sequencing (RNA-Seq) to evaluate the profiling of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs). Bioinformatics analysis was performed to predict the potential NaB-related lncRNAs and genes in DN. The expressions of lncRNAs and mRNAs were tested using the quantitative real-time polymerase chain reactions (qRT-PCRs) in renal tissues and mesangial cells treated with NaB. The results of the present study demonstrated that NaB ameliorated renal dysfunction in DN mice. Moreover, RNA-Seq results identified that some lncRNAs and mRNAs were reversely changed in the DN+NaB group in comparison to those in the DN group. Additionally, the integrated co-expression networks of NaB-related lncRNAs revealed that these lncRNAs interacted with 155 key mRNAs. Furthermore, the co-expression network of inflammation-related lncRNAs and mRNAs demonstrated that those reversed lncRNAs and mRNAs also play essential roles in the inflammatory response. In summary, the present study suggests that NaB ameliorates diabetes-induced renal dysfunction and regulates transcriptome changes in DN.