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CircRNA Galntl6 sponges miR-335 to ameliorate stress-induced hypertension through upregulating Lig3 in rostral ventrolateral medulla
Redox Biology ( IF 10.7 ) Pub Date : 2023-06-09 , DOI: 10.1016/j.redox.2023.102782
Shuai Zhang 1 , Xueping Wang 2 , Gaojun Chen 2 , Lei Tong 2 , Tengteng Dai 2 , Linping Wang 2 , Liucun Zhu 2 , Haili Zhang 3 , Dongshu Du 4
Affiliation  

Rostral ventrolateral medulla (RVLM) is thought to serve as a major vasomotor center that participates in controlling the progression of stress-induced hypertension (SIH). Circular RNAs (circRNAs) perform important functions in the regulation of diverse physiological and pathological processes. However, information concerning the functions of RVLM circRNAs on SIH remains limited. RNA sequencing was performed to profile circRNA expression in RVLMs from SIH rats, which were induced by electric foot shocks and noises. The functions of circRNA Galntl6 in reducing blood pressure (BP) and its potential molecular mechanisms on SIH were investigated via various experiments, such as Western blot and intra-RVLM microinjection. A total of 12,242 circRNA transcripts were identified, among which circRNA Galntl6 was dramatically downregulated in SIH rats. The upregulation of circRNA Galntl6 in RVLM effectively decreased the BP, sympathetic outflow, and neuronal excitability in SIH rats. Mechanistically, circRNA Galntl6 directly sponged microRNA-335 (miR-335) and restrained it to reduce oxidative stress. Reintroduction of miR-335 observably reversed the circRNA Galntl6-induced attenuation of oxidative stress. Furthermore, Lig3 can be a direct target of miR-335. MiR-335 inhibition substantially increased the expression of Lig3 and suppressed oxidative stress, and these favorable effects were blocked by Lig3 knockdown. CircRNA Galntl6 is a novel factor that impedes SIH development, and the circRNA Galntl6/miR-335/Lig3 axis represents one of the possible mechanisms. These findings demonstrated circRNA Galntl6 as a possibly useful target for the prevention of SIH.



中文翻译:


CircRNA Galntl6 海绵 miR-335 通过上调延髓头端腹外侧 Lig3 改善应激性高血压



延髓头侧腹外侧 (RVLM) 被认为是参与控制应激性高血压 (SIH) 进展的主要血管舒缩中心。环状RNA(circRNA)在调节多种生理和病理过程中发挥重要功能。然而,有关 RVLM circRNA 在 SIH 中的功能的信息仍然有限。通过 RNA 测序来分析 SIH 大鼠 RVLM 中的 circRNA 表达,这些大鼠是由足部电击和噪音诱导的。通过蛋白质印迹和RVLM内显微注射等多种实验研究了circRNA Galntl6在降低血压(BP)中的功能及其对SIH的潜在分子机制。总共鉴定了 12,242 个 circRNA 转录本,其中 circRNA Galntl6 在 SIH 大鼠中显着下调。 RVLM 中 circRNA Galntl6 的上调可有效降低 SIH 大鼠的血压、交感神经流出和神经元兴奋性。从机制上讲,circRNA Galntl6 直接吸收 microRNA-335 (miR-335) 并抑制它以减少氧化应激。重新引入 miR-335 可明显逆转 circRNA Galntl6 诱导的氧化应激减弱。此外,Lig3 可以是 miR-335 的直接靶标。 MiR-335 抑制显着增加了 Lig3 的表达并抑制了氧化应激,而这些有利的作用被 Lig3 敲低所阻断。 CircRNA Galntl6 是一种阻碍 SIH 发展的新因子,circRNA Galntl6/miR-335/Lig3 轴代表了可能的机制之一。这些发现证明 circRNA Galntl6 可能是预防 SIH 的有用靶点。

更新日期:2023-06-12
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