Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys
Anish Jain1, Hyun Jun Jung2, Joseph Aubee3
1Department of Physiology, Howard University College of Medicine, Washington, DC 20059, USA.
Biomolecules
|September 28, 2024
Summary
Loss of sodium hydrogen exchanger 1 (NHERF1) in mice kidneys leads to increased cytokine expression via miR-153 and NFATc2/NFATc3. This study reveals NHERF1
Area of Science:
- Nephrology
- Molecular Biology
- Aging Research
Background:
- MicroRNAs (miRNAs) regulate cellular functions, but their role in kidney aging is not fully understood.
- Sodium hydrogen exchanger 1 (NHERF1) influences cellular responses, hypertension, and transporter trafficking, but its regulatory mechanisms remain unclear.
- NHERF1's role in miRNA-mediated gene networks, particularly in kidney aging and fibrosis, requires investigation.
Purpose of the Study:
- To investigate the impact of NHERF1 expression on miRNA profiles in aging mouse kidneys.
- To explore the hypothesis that NHERF1 dysregulates miRNA networks, inducing kidney fibrosis and cytokine expression.
- To elucidate the molecular mechanisms linking NHERF1, miRNAs, and cytokine production in kidney aging.
Main Methods:
- Comparison of miRNA expression in kidneys of young and old wild-type (WT) and NHERF1 knockout (NHERF1-/-) mice.
- Analysis of transcription factors NFATc2 and NFATc3 expression using immunohistochemistry and western blotting.
- Quantification of cytokine expression (IL-1β, IL-6, IL-17A, MCP1, TNF-α) in mouse kidney tissues.
Main Results:
- NHERF1 deficiency significantly altered miRNA expression, with miR-153 notably decreased.
- miR-153 was identified to downregulate NFATc2 and NFATc3, transcription factors for cytokines.
- Old NHERF1-/- mice exhibited increased nuclear NFATc2/NFATc3 and elevated levels of pro-inflammatory cytokines.
Conclusions:
- Loss of NHERF1 expression in aging kidneys promotes cytokine production.
- This effect is mediated by the interactive regulation between miR-153 and NFATc2/NFATc3.
- NHERF1 plays a critical role in maintaining kidney homeostasis during aging by modulating miRNA-cytokine pathways.
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