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Abstract：
The rostral ventrolateral medulla (RVLM) is an essential vasomotor center responsible for regulating the development of stress-induced hypertension (SIH). Long non-coding RNAs (lncRNAs) play critical roles in various physiopathology processes, but existing research on the functions of RVLM lncRNAs on SIH has been lacking. In this study, we investigated the roles of RVLM lncRNAs in SIH.
Genome-wide lncRNA profiles in RVLM were determined by RNA sequencing in a SIH rat model established using electric foot shocks plus noises. The hypotensive effect of lncRNA INPP5F and the underlying mechanisms of lncRNA INPP5F on SIH were explored through in vivo and in vitro experiments, such as intra-RVLM microinjection and immunofluorescence.
We discovered 10,179 lncRNA transcripts, among which the lncRNA INPP5F expression level was significantly decreased in SIH rats. Overexpression of lncRNA INPP5F in RVLM dramatically reduced the blood pressure, sympathetic nerve activity, and neuronal excitability of SIH rats. LncRNA INPP5F overexpression markedly increased Cttn expression and reduced neural apoptosis by activating the PI3K-AKT pathway, and its inhibition had opposite effects. Mechanistically, lncRNA INPP5F acted as a sponge of miR-335, which further regulated the Cttn expression.
LncRNA INPP5F was a key factor that inhibited SIH progression, and the identified lncRNA INPP5F/miR-335/Cttn/PI3K-AKT/apoptosis axis represented one of the possible mechanisms. LncRNA INPP5F could serve as a therapeutic target for SIH.
Genome-wide lncRNA profiles in RVLM were determined by RNA sequencing in a SIH rat model established using electric foot shocks plus noises. The hypotensive effect of lncRNA INPP5F and the underlying mechanisms of lncRNA INPP5F on SIH were explored through in vivo and in vitro experiments, such as intra-RVLM microinjection and immunofluorescence.
We discovered 10,179 lncRNA transcripts, among which the lncRNA INPP5F expression level was significantly decreased in SIH rats. Overexpression of lncRNA INPP5F in RVLM dramatically reduced the blood pressure, sympathetic nerve activity, and neuronal excitability of SIH rats. LncRNA INPP5F overexpression markedly increased Cttn expression and reduced neural apoptosis by activating the PI3K-AKT pathway, and its inhibition had opposite effects. Mechanistically, lncRNA INPP5F acted as a sponge of miR-335, which further regulated the Cttn expression.
LncRNA INPP5F was a key factor that inhibited SIH progression, and the identified lncRNA INPP5F/miR-335/Cttn/PI3K-AKT/apoptosis axis represented one of the possible mechanisms. LncRNA INPP5F could serve as a therapeutic target for SIH.
摘要：
目的：延髓腹外侧端（RVLM）是一个重要的血管舒缩中枢，负责调节应激性高血压（SIH）的发展。长链非编码RNA（lncRNAs）在各种病理生理过程中发挥关键作用，但是现有的关于RVLMlncRNAs在SIH上的功能研究一直缺乏。在这项研究中,我们研究了RVLMlncRNAs在SIH中的作用。
方法：在使用电击和噪声建立的SIH大鼠模型中，通过RNA测序确定RVLM中的全基因组lncRNA谱。通过体内和体外实验探讨了lncRNAINPP5F的降压作用和lncRNAINPP5F对SIH的潜在机制，例如RVLM内显微注射和免疫荧光。
结果：我们发现了10,179个lncRNA转录本，其中lncRNAINPP5F在SIH大鼠中的表达水平显著降低。在RVLM中lncRNAINPP5F的过表达显著降低了血压，交感神经活动，和SIH大鼠的神经元兴奋性。LncRNAINPP5F过表达通过激活PI3K-AKT通路显著增加Cttn表达并减少神经细胞凋亡,其抑制作用具有相反的效果。机械上,lncRNAINPP5F充当miR-335的海绵，进一步调控Cttn的表达。
结论：LncRNAINPP5F是抑制SIH进展的关键因素，和鉴定的lncRNAINPP5F/miR-335/Cttn/PI3K-AKT/凋亡轴代表了可能的机制之一。LncRNAINPP5F可以作为SIH的治疗靶标。
方法：在使用电击和噪声建立的SIH大鼠模型中，通过RNA测序确定RVLM中的全基因组lncRNA谱。
结果：我们发现了10,179个lncRNA转录本，
结论：LncRNAINPP5F是抑制SIH进展的关键因素，
