液泡膜蛋白1与肾缺血和缺血/再灌注的急性反应。

IF 2.5 4区 生物学 Q3 CELL BIOLOGY
Physiological genomics Pub Date : 2025-03-01 Epub Date: 2025-02-10 DOI:10.1152/physiolgenomics.00135.2024
Vaishali Singh, Ryan J Adam, Mark R Paterson, Alison J Kriegel
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引用次数: 0

摘要

缺血再灌注(I/R)损伤是慢性肾脏疾病和肾功能衰竭的重要始发原因。近端小管(PT)形态的改变,包括刷状边界的丧失,在缺血应激和I/R损伤的反应中迅速发生。液泡膜蛋白1 (VMP1)是缺血相关性肾损伤的一个引人注目的靶标,因为它是自噬的必要调节剂,并且缺氧反应的microRNA miR-21的基因组位置位于VMP1基因的内含子区域。据报道,自噬对I/R损伤具有保护和病理作用。在本研究中,我们发现肾皮质组织在缺血15和30分钟后VMP1迅速上调。在成年雄性Sprague Dawley大鼠肾缺血30分钟、缺血30分钟后再灌注24小时(I/R)或相应的对照程序之前,静脉注射靶向vmp1的GapmeR或重组GapmeR 2天。观察肾皮质自噬标志物及PT形态学变化。抑制缺血诱导的VMP1上调可减轻缺血30分钟和i /R后24小时的PT刷边损失。我们的研究揭示了VMP1表达、miR-21-5p表达、自噬标记物和肾皮质I/R小管损伤之间一种新的、机制上重要的分离。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Vacuole membrane protein 1 and acute response to renal ischemia and ischemia/reperfusion.

Ischemia-reperfusion (I/R) injury is an important initiating cause of chronic kidney disease and renal failure. Changes in proximal tubule (PT) morphology, including brush border loss, occur rapidly in response to ischemic stress and I/R injury. Vacuole membrane protein 1 (VMP1) is a compelling target for ischemia-associated renal damage because it is a necessary regulator of autophagy, and the genomic location of hypoxia-responsive microRNA miR-21 lies within an intronic region of the Vmp1 gene. Autophagy is reported to have protective and pathological effects on I/R injury. In this study, we find that VMP1 is rapidly upregulated in renal cortex tissue in response to 15 and 30 min of ischemia. Intravenous delivery of Vmp1-targeting GameR or a scrambled GapmeR was performed on adult male Sprague-Dawley rats for 2 days before either 30 min of renal ischemia, 30 min of ischemia followed by 24 h of reperfusion (I/R), or corresponding control procedures. Autophagy markers and PT morphology were assessed in the renal cortex. Suppression of ischemia-induced upregulation of VMP1 attenuated PT brush border loss following 30 min of ischemia and 24 h post-I/R. Our study reveals a novel and mechanistically important dissociation between VMP1 expression, miR-21-5p expression, autophagy markers, and I/R tubular injury in the renal cortex.NEW & NOTEWORTHY The impact of autophagy on renal ischemia/reperfusion injury (IRI) remains unclear. VMP1 promotes autophagy through interaction with beclin-1 and subsequent localization to the endoplasmic reticulum. In this study, GapmeR-mediated suppression of VMP1 in rats and attenuated proximal tubule damage following 30 min of ischemia or following 24 h of reperfusion, without altering autophagy markers following reperfusion. This new insight suggests that increased VMP1 did not afford autophagy-mediated protection from IRI in proximal tubules.

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来源期刊
Physiological genomics
Physiological genomics 生物-生理学
CiteScore
6.10
自引率
0.00%
发文量
46
审稿时长
4-8 weeks
期刊介绍: The Physiological Genomics publishes original papers, reviews and rapid reports in a wide area of research focused on uncovering the links between genes and physiology at all levels of biological organization. Articles on topics ranging from single genes to the whole genome and their links to the physiology of humans, any model organism, organ, tissue or cell are welcome. Areas of interest include complex polygenic traits preferably of importance to human health and gene-function relationships of disease processes. Specifically, the Journal has dedicated Sections focused on genome-wide association studies (GWAS) to function, cardiovascular, renal, metabolic and neurological systems, exercise physiology, pharmacogenomics, clinical, translational and genomics for precision medicine, comparative and statistical genomics and databases. For further details on research themes covered within these Sections, please refer to the descriptions given under each Section.
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