在大鼠模型中,HIV1-Nef干扰了血睾屏障的完整性。

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Tissue Barriers Pub Date : 2024-05-22 DOI:10.1080/21688370.2024.2357406
Deependra Singh, Saurabh Kumar, Rajnikant Mishra, Anjali, R K Tripathi, Monika Sachdev
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引用次数: 0

摘要

血睾屏障是哺乳动物睾丸内的一个特殊特征,它紧邻曲细精管的基底膜。这道屏障将曲细精管上皮细胞分为不同的基底区和顶端区。BTB 对外来颗粒的选择性使其成为病毒的安全避难所,而 HIV 对睾丸的高亲和力可能会导致病毒的垂直传播。本研究通过静脉注射重组 HIV1-Nef 蛋白(rNef)来研究 rNef 对 BTB 的影响。SD 雄性大鼠通过尾静脉分别接受了 250 µg 和 500 µg 的 rNef 以及 2% 的埃文斯蓝染料(1 ml)。灌注 1 小时后,动物被处死以进行分析。染料迁移试验和酶联免疫吸附试验分别证实了血睾屏障(BTB)的明显受损和 rNef 在睾丸组织中的表现。此外,在rNef诱导的BTB破坏过程中,还观察到包括ZO1和Occludin在内的紧密连接蛋白的表达下降。总之,我们的研究结果表明,rNef通过各种信号事件诱导BTB破坏。在曲细精管上皮的外质特化部位,发现粘连蛋白的定位被破坏,从而使睾丸成为一个易受攻击的部位。总之,rNef干扰了大鼠模型中血睾屏障的完整性;因此,它也可以作为研究血睾屏障动态的合适模型。
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HIV1-Nef perturbs the integrity of blood testis barrier in rat model.

The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.

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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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