Inner Mongolia Key Laboratory of Bio-manufacture, Inner Mongolia Agricultural University, Hohhot, China.
College of Life Sciences, Inner Mongolia Agricultural University, Hohhot, China.
FEBS Open Bio. 2022 Apr;12(4):864-876. doi: 10.1002/2211-5463.13380. Epub 2022 Feb 22.
Salt dietary intake is tightly coupled to human health, and excessive sodium can cause strokes and cardiovascular diseases. Research into the renal medulla of camels exhibiting high salt resistance may aid identification of the mechanisms governing resistance to high salinity. In this study, we used RNA sequencing (RNA-seq) to show that in the renal medulla of camels under salt stress, 22 mRNAs, 2 long noncoding RNAs (lncRNAs), and 31 microRNAs (miRNAs) exhibited differential expression compared with the free salt-intake diet group. Using fluorescence in situ hybridization and dual-luciferase reporter assays, we demonstrated that the lncRNA LNC003834 can bind miRNA-34a and thereby relieve suppression of the salt-absorption-inhibiting SLC14A1 mRNA from miRNA-34a, suggesting that the above lncRNA-miRNA-mRNA act as competing endogenous RNAs (ceRNAs). We subsequently performed short hairpin RNA and small RNA interference and reactive oxygen species (ROS) detection assays to show that SLC6A1, PCBP2, and PEX5L can improve the antioxidation capacity of renal medulla cells of camel by decreasing ROS levels. Our data suggest that camels achieve sodium homeostasis through regulating the expression of salt-reabsorption-related genes in the renal medulla, and this involves ceRNAs (SLC14A1 mRNA, LNC003834, and miRNA-34a) and antioxidant genes (SLC6A1, PCBP2, and PEX5L). These data may assist in the development of treatments for diseases induced by high salt diets.
盐的摄入与人类健康密切相关，过量的钠会导致中风和心血管疾病。研究骆驼肾髓质对高盐的抗性，可以帮助确定高盐抗性的机制。在这项研究中，我们使用 RNA 测序（RNA-seq）显示，在盐胁迫下骆驼肾髓质中，有 22 个 mRNA、2 个长非编码 RNA（lncRNA）和 31 个 microRNA（miRNA）与自由摄盐饮食组相比表现出差异表达。通过荧光原位杂交和双荧光素酶报告基因检测，我们证明 lncRNA LNC003834 可以与 miRNA-34a 结合，从而解除 miRNA-34a 对盐吸收抑制 SLC14A1 mRNA 的抑制作用，表明上述 lncRNA-miRNA-mRNA 作为竞争内源 RNA（ceRNA）发挥作用。随后，我们进行了短发夹 RNA 和小 RNA 干扰以及活性氧（ROS）检测实验，表明 SLC6A1、PCBP2 和 PEX5L 可以通过降低 ROS 水平来提高骆驼肾髓质细胞的抗氧化能力。我们的数据表明，骆驼通过调节肾髓质中盐吸收相关基因的表达来实现钠稳态，这涉及 ceRNA（SLC14A1 mRNA、LNC003834 和 miRNA-34a）和抗氧化基因（SLC6A1、PCBP2 和 PEX5L）。这些数据可能有助于开发高盐饮食诱导疾病的治疗方法。
