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Volume 14
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10.3390/biom14091048
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Article

Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys

by
Anish Jain
1,†,
Hyun Jun Jung
2,†,
Joseph Aubee
3,
Jahn N. O’Neil
1,
Laila A. Muhammad
1,
Shaza Khan
1,
Karl Thompson
3,
Maurice B. Fluitt
4,
Dexter L. Lee
1,
Carolyn M. Klinge
5 and
Syed J. Khundmiri
1,*
1
Department of Physiology, Howard University College of Medicine, Washington, DC 20059, USA
2
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3
Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA
4
Department of Medicine, Howard University College of Medicine, Washington, DC 20059, USA
5
Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40202, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2024, 14(9), 1048; https://doi.org/10.3390/biom14091048
Submission received: 29 July 2024 / Revised: 19 August 2024 / Accepted: 20 August 2024 / Published: 23 August 2024
(This article belongs to the Section Biomacromolecules: Nucleic Acids)
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Abstract

MicroRNAs (miRNAs) play important roles in the regulation of cellular function and fate via post-transcriptional regulation of gene expression. Although several miRNAs are associated with physiological processes and kidney diseases, not much is known about changes in miRNAs in aging kidneys. We previously demonstrated that sodium hydrogen exchanger 1 (NHERF1) expression regulates cellular responses to cisplatin, age-dependent salt-sensitive hypertension, and sodium-phosphate cotransporter trafficking. However, the mechanisms driving these regulatory effects of NHERF1 on cellular processes are unknown. Here, we hypothesize that dysregulation of miRNA-mediated gene regulatory networks that induce fibrosis and cytokines may depend on NHERF1 expression. To address this hypothesis, we compared miRNA expression in kidneys from both male and female old (12–18-month-old) and young (4–7-month-old) wild-type (WT) and NHERF1 knockout (NHERF1−/−) mice. Our results identified that miRNAs significantly decreased in NHERF1−/− mice included miR-669m, miR-590-3p, miR-153, miR-673-3p, and miR-127. Only miR-702 significantly decreased in aged WT mice, while miR-678 decreased in both WT and NHERF1−/− old versus young mice. miR-153 was shown to downregulate transcription factors NFATc2 and NFATc3 which regulate the transcription of several cytokines. Immunohistochemistry and western blotting revealed a significant increase in nuclear NFATc2 and NFATc3 in old NHERF1−/− mice compared to old WT mice. Our data further show that expression of the cytokines IL-1β, IL-6, IL-17A, MCP1, and TNF-α significantly increased in the old NHERF1−/− mice compared to the WT mice. We conclude that loss of NHERF1 expression induces cytokine expression in the kidney through interactive regulation between miR-153 and NFATc2/NFATc3 expression.
Keywords: sodium-hydrogen exchanger regulatory factor-1; kidneys; aging; miRNA; miR-153; nuclear factor of activated T-cells (NFATc2/3) sodium-hydrogen exchanger regulatory factor-1; kidneys; aging; miRNA; miR-153; nuclear factor of activated T-cells (NFATc2/3)

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MDPI and ACS Style

Jain, A.; Jung, H.J.; Aubee, J.; O’Neil, J.N.; Muhammad, L.A.; Khan, S.; Thompson, K.; Fluitt, M.B.; Lee, D.L.; Klinge, C.M.; et al. Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys. Biomolecules 2024, 14, 1048. https://doi.org/10.3390/biom14091048

AMA Style

Jain A, Jung HJ, Aubee J, O’Neil JN, Muhammad LA, Khan S, Thompson K, Fluitt MB, Lee DL, Klinge CM, et al. Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys. Biomolecules. 2024; 14(9):1048. https://doi.org/10.3390/biom14091048

Chicago/Turabian Style

Jain, Anish, Hyun Jun Jung, Joseph Aubee, Jahn N. O’Neil, Laila A. Muhammad, Shaza Khan, Karl Thompson, Maurice B. Fluitt, Dexter L. Lee, Carolyn M. Klinge, and et al. 2024. "Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys" Biomolecules 14, no. 9: 1048. https://doi.org/10.3390/biom14091048

APA Style

Jain, A., Jung, H. J., Aubee, J., O’Neil, J. N., Muhammad, L. A., Khan, S., Thompson, K., Fluitt, M. B., Lee, D. L., Klinge, C. M., & Khundmiri, S. J. (2024). Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys. Biomolecules, 14(9), 1048. https://doi.org/10.3390/biom14091048

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