睾丸特异性蛋白Y编码样2激活下丘脑室旁核的JAK2/STAT3通路,从而维持高血压。

IF 3.2 3区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Ying Li, Yang-Fei Xu, Hong-Li Chi, Jia-Yue Yu, Ya-Nan Gao, Hong-Bao Li, Yu-Ming Kang, Xiao-Jing Yu
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引用次数: 0

摘要

背景:与血压正常的 Wistar-Kyoto 大鼠(WKY)相比,自发性高血压大鼠(SHRs)下丘脑室旁核(PVN)中睾丸特异性蛋白 Y 编码样 2(TSPYL2)的表达量和 Janus 激酶 2(JAK2)/信号转导及激活剂转录 3(STAT3)的磷酸化水平较高。但它们是如何参与高血压的仍不清楚。TSPYL2可能与PVN中的JAK2/STAT3相互作用,维持高血压期间的高血压:方法:通过将携带 shRNA 的腺相关病毒(AAV)微注射到 SHR 和 WKY 大鼠的 PVN 中,对 TSPYL2 进行基因敲除。SHR大鼠腹腔注射或PVN注射AG490以抑制JAK2/STAT3。测量了血压(BP)、血浆去甲肾上腺素(NE)、PVN炎症反应和PVN氧化应激:结果:敲除SHR PVN中的TSPYL2会导致血压和血浆去甲肾上腺素降低,JAK2/STAT3失活,促炎细胞因子IL-1β表达减少,抗炎细胞因子IL-10表达增加。同时,以两种方式给药的 AG490 可降低 SHR 的血压,并使 JAK2/STAT3 失活,但未能改变 PVN 中 TSPYL2 的表达。AG490 还能下调 IL-1β 的表达,上调 IL-10 的表达。敲除TSPYL2和抑制JAK2/STAT3都能减轻SHR PVN中的氧化应激:结论:JAK2/STAT3在SHR PVN中受TSPYL2调控,而PVN TSPYL2/JAK2/STAT3对维持高血压大鼠的高血压至关重要,因此是高血压的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Testis-Specific Protein, Y-Encoded-Like 2 Activates JAK2/STAT3 Pathway in Hypothalamic Paraventricular Nucleus to Sustain Hypertension.

Background: In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of the testis-specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain high blood pressure during hypertension.

Methods: Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral microinjection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured.

Results: TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1β, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the BP in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1β and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs.

Conclusion: JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high BP in hypertensive rats, making it a potential therapeutic target for hypertension.

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来源期刊
American Journal of Hypertension
American Journal of Hypertension 医学-外周血管病
CiteScore
6.90
自引率
6.20%
发文量
144
审稿时长
3-8 weeks
期刊介绍: The American Journal of Hypertension is a monthly, peer-reviewed journal that provides a forum for scientific inquiry of the highest standards in the field of hypertension and related cardiovascular disease. The journal publishes high-quality original research and review articles on basic sciences, molecular biology, clinical and experimental hypertension, cardiology, epidemiology, pediatric hypertension, endocrinology, neurophysiology, and nephrology.
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