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Single-nucleus RNA sequencing reveals loss of DCT1 renal tubules in HIV Vpr transgenic mice

  1. Author:
    Latt, Khun Zaw
    Yoshida, Teruhiko
    Shrivastav, Shashi
    Abedini, Amin
    Reece, Jeff M
    Sun, Zeguo
    Lee, Hewang
    Okamoto, Koji
    Dagur, Pradeep
    Ishimoto, Yu
    Heymann, Jurgen
    Zhao,Yongmei
    Chung, Joon-Yong
    Hewitt, Stephen
    Jose, Pedro A
    Lee, Kyung
    He, John Cijiang
    Winkler,Cheryl
    Knepper, Mark A
    Kino, Tomoshige
    Rosenberg, Avi Z
    Susztak, Katalin
    Kopp, Jeffrey B

  2. Author Address

    Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD. Electronic address: khunzaw.latt@nih.gov., Department of Medicine, Renal Electrolyte and Hypertension Division; Institute for Diabetes, Obesity, and Metabolism; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Advanced Light Microscopy & Image Analysis Core (ALMIAC), NIDDK, NIH, Bethesda, MD., Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Departments of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC., Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD; Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan., Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Polycystic Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD., Advanced Biomedical and Computational Sciences, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., NCI, Frederick, MD., Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD., Departments of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC; Departments of Physiology and Pharmacology, The George Washington University School of Medicine & Health Sciences, Washington, DC., Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute and Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, MD., Epithelial Systems Biology Laboratory, Systems Biology Center, Division of Intramural Research, NHLBI, NIH, Bethesda, MD., Laboratory for Molecular and Genomic Endocrinology, Division of Translational Medicine, Sidra Medicine, Doha, Qatar., Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD., Kidney Disease Section, Kidney Diseases Branch, NIDDK, NIH, Bethesda MD. Electronic address: jeffreyk@intra.niddk.nih.gov.,
    1. Year: 2024
    2. Date: Jul 18
    3. Epub Date: 2024 07 18
  2. Journal: The American Journal of Pathology
  4. Type of Article: Article
  1. Abstract:

    Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its 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 Na-Cl 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 results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that 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 WT mice (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3+Pvalb+ DCT1 segments in Vpr Tg mice. Differential gene expression analysis between Vpr Tg and WT in the DCT cluster showed downregulation of 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 downregulation in DCT1 cells and loss of Slc12a3+Pvalb+ DCT1 segments. Copyright © 2024. Published by Elsevier Inc.

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  2. DOI: 10.1016/j.ajpath.2024.06.006
  3. PMID: 39032602
  4. PII : S0002-9440(24)00237-2

Library Notes

  1. Fiscal Year: FY2023-2024
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