单核 RNA 测序揭示了 HIV Vpr 转基因小鼠肾小管 DCT1 的缺失。

IF 4.7 2区 医学 Q1 PATHOLOGY
Khun Zaw Latt , Teruhiko Yoshida , Shashi Shrivastav , Amin Abedini , Jeff M. Reece , Zeguo Sun , Hewang Lee , Koji Okamoto , Pradeep Dagur , Yu Ishimoto , Jurgen Heymann , Yongmei Zhao , Joon-Yong Chung , Stephen Hewitt , Pedro A. Jose , Kyung Lee , John Cijiang He , Cheryl A. Winkler , Mark A. Knepper , Tomoshige Kino , Jeffrey B. Kopp
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引用次数: 0

摘要

低钠血症和盐丢失是艾滋病毒/艾滋病患者的常见病,但人们对其诱因的了解却很有限。艾滋病毒病毒蛋白 R(Vpr)是导致艾滋病毒相关性肾病的原因之一。为了研究 Vpr 对远端肾小管的影响以及对编码 Na-Cl 共转运体(负责远端肾小管钠重吸收)的 Slc12a3 基因表达水平的影响,研究人员对三只野生型(WT)和三只 Vpr 转基因(Vpr Tg)小鼠的肾皮质进行了单核 RNA 测序。结果表明,与 WT 小鼠相比,Vpr Tg 小鼠远端曲小管(DCT)细胞的百分比明显降低(P < 0.05),而在 Vpr Tg 小鼠中,DCT 细胞中 Slc12a3 的表达无明显差异。与 WT 小鼠相比,Vpr Tg 小鼠中 Pvalb+ DCT1 亚簇细胞较少(P < 0.01)。免疫组化显示,Vpr Tg 小鼠的 Slc12a3+Pvalb+ DCT1 区段较少。Vpr Tg 和 WT 在 DCT 簇中的差异基因表达分析表明,Ier3 基因下调,而 Ier3 是一种细胞凋亡抑制因子。通过 siRNA 转染体外敲除 Ier3 可诱导小鼠 DCT 细胞凋亡。这些观察结果表明,Vpr对Vpr Tg小鼠的盐耗效应可能是由DCT1细胞中的Ier3下调和Slc12a3+Pvalb+ DCT1区段的缺失介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice

Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice
Although hyponatremia and salt wasting are common in patients with HIV/AIDS, the understanding of their contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the Slc12a3 gene, encoding the sodium-chloride cotransporter (which is responsible for sodium reabsorption in distal nephron segments), single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr transgenic (Vpr Tg) mice. The percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05); in Vpr Tg mice, Slc12a3 expression was not significantly different in DCT cells. The Pvalb+ DCT1 subcluster had fewer cells in Vpr Tg mice compared with those in WT mice (P < 0.01). Immunohistochemistry revealed fewer Slc12a3+ Pvalb+ DCT1 segments in Vpr Tg mice. Differential gene expression analysis between Vpr Tg and WT samples in the DCT cluster showed down-regulation of the Ier3 gene, which is an inhibitor of apoptosis. The in vitro knockdown of Ier3 by siRNA transfection induced apoptosis in mouse DCT cells. These observations suggest that the salt-wasting effect of Vpr in Vpr Tg mice is likely mediated by Ier3 down-regulation in DCT1 cells and loss of Slc12a3+ Pvalb+ DCT1 segments.
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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