Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Center for Translational Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Pediatr Res. 2023 May;93(6):1509-1518. doi: 10.1038/s41390-022-02228-z. Epub 2022 Aug 19.
Urinary tract obstruction is a common cause of renal failure in children and infants, and the pathophysiological mechanisms of obstructive nephropathy are largely unclear. It has been reported that m6A modulation is involved in renal injury. However, whether m6A RNA modulation is associated with obstructive nephropathy has not yet been reported. The aim of this study was to investigate the m6A epitranscriptome profiles in the kidneys of bilateral ureteral obstruction (BUO) in young rats.
The total level of m6A in the kidneys was measured by liquid chromatography-tandem mass spectrometry. The mRNAs of related genes were detected by real-time PCR. Methylated RNA immunoprecipitation sequencing was performed to map the epitranscriptome-wide m6A profile.
Global m6A levels were increased after BUO, and the mRNA expression levels of m6A methyltransferases and demethylases were significantly decreased in BUO group rat kidneys; the expression levels of EGFR and Brcal were significantly upregulated, while the mRNA expression levels of Notch1 were downregulated (P < 0.05). A total of 154 genes associated with 163 m6A peaks were identified.
The m6A epitranscriptome was significantly altered in BUO rat kidneys, which is potentially implicated in the pathophysiological processes of obstructive nephropathy.
The m6A RNA modification was associated with the process of renal injury in ureteral obstructive nephropathy by participating in multiple dimensions. The dysregulation of m6A methyltransferases and demethylases may be related to the pathophysiological changes of BUO-induced obstructive nephropathy. The m6A RNA modulation of the genes EGFR, Brca1, and Notch1 that were related to the regulation of aquaporin2 might be the potential mechanism for the polyuresis after ureteral obstruction.
尿路梗阻是儿童和婴儿肾衰竭的常见原因，梗阻性肾病的病理生理机制在很大程度上尚不清楚。据报道，m6A 调节参与了肾损伤。然而，m6A RNA 调节是否与梗阻性肾病有关尚未报道。本研究旨在探讨双侧输尿管梗阻（BUO）幼鼠肾脏中 m6A 转录组谱的变化。
通过液相色谱-串联质谱法测定肾脏中 m6A 的总水平。实时 PCR 检测相关基因的 mRNA。通过甲基化 RNA 免疫沉淀测序绘制全转录组范围的 m6A 图谱。
BUO 后整体 m6A 水平升高，BUO 组大鼠肾脏中 m6A 甲基转移酶和去甲基化酶的 mRNA 表达水平明显降低；EGFR 和 Brcal 的表达水平明显上调，而 Notch1 的 mRNA 表达水平下调（P<0.05）。共鉴定出 154 个与 163 个 m6A 峰相关的基因。
BUO 大鼠肾脏的 m6A 转录组发生了显著改变，这可能与梗阻性肾病的病理生理过程有关。
m6A RNA 修饰通过参与多个维度与输尿管梗阻性肾病肾损伤过程有关。m6A 甲基转移酶和去甲基化酶的失调可能与 BUO 诱导的梗阻性肾病的病理生理变化有关。与水通道蛋白 2 调节相关的基因 EGFR、Brca1 和 Notch1 的 m6A RNA 修饰可能是输尿管梗阻后多尿的潜在机制。
