miRNA-23a modulates sodium-hydrogen exchanger 1 expression: studies in medullary thick ascending limb of salt-induced hypertensive rats
Abstract
Background The kidney is the main organ in the pathophysiology of essential hypertension. Although most bicarbonate reabsorption occurs in the proximal tubule, the medullary thick ascending limb (mTAL) of the nephron also maintains acid-base balance by contributing to 25% of bicarbonate reabsorption. A crucial element in this regulation is the sodium-hydrogen exchanger 1 (NHE1), a ubiquitous membrane protein controlling intracellular pH, where proton extrusion is driven by the inward sodium flux. MicroRNA (miRNA) expression of hypertensive patients significantly differs from that of normotensive subjects. The aim of this study was to determine the functional role of miRNA alterations at the mTAL level. Methods By miRNA microarray analysis, we identified miRNA expression profiles in isolated mTALs from high sodium intake-induced hypertensive rats (HSD) versus their normotensive counterparts (NSD). In vitro validation was carried out in rat mTAL cells. Results Five miRNAs involved in the onset of salt-sensitive hypertension were identified, including miR-23a, which was bioinformatically predicted to target NHE1 mRNA. Data demonstrated that miRNA-23a is downregulated in the mTAL of HSD rats while NHE1 is upregulated. Consistently, transfection of an miRNA-23a mimic in an mTAL cell line, using a viral vector, resulted in NHE1 downregulation. Conclusion NHE1, a protein involved in sodium reabsorption at the mTAL level and blood pressure regulation, is upregulated in our model. Thi…
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In hypertensive rats, miR-23a can regulate acid-base balance in the kidney through the target gene NHE1.
“In hypertensive rats, it can regulate acid-base balance in the kidney through the target gene sodium hydrogen exchanger 1 (NHE1) [69].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [69]
miR-23a belongs to one of the miRNAs related to the pathogenesis of salt sensitive hypertension.
“Meanwhile, miR-23a belongs to one of the miRNAs related to the pathogenesis of salt sensitive hypertension.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [69]
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Recent advances of miR-23 in human diseases and growth development
Qian, X., Jiang, Y., Yang, Y., Zhang, Y., Xu, N., Xu, B., Pei, K., Yu, Z., & Wu, W. (2025) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.12.010 · Cited by 5 · see citing works
- Authors
- Lombari, P., Mallardo, M., Petrazzuolo, O., Amruthraj Nagoth, J., Fiume, G., Scanni, R., Iervolino, A., Damiano, S., Coppola, A., Borriello, M., Ingrosso, D., Perna, A. F., Zacchia, M., Trepiccione, F., & Capasso, G.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- University of Naples Federico II (IT)
- Division of Nephrology, Department of Translational Medical Sciences, University of Campania “L. Vanvitelli” , Naples , Italy
- Magna Graecia University (IT)
- Biogem (IT)
- Corresponding author
- Lombari, Patrizia
- Mallardo, Massimo
- ORCID
- Venue
- Nephrology Dialysis Transplantation
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-08-03
- Volume
- 38
- Issue
- 3
- Pages
- 586-598
- ISSN
- 0931-0509 (ISSN-L)
- 1460-2385
- OpenAlex
- W4289638049
- Cited by
- 4
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Nephrology Dialysis Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Funders
- Italian Ministry of University and Research (2006065339)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- miR-23a, NHE1, medullary thick ascending limb, salt-sensitive hypertension, high sodium intake, bicarbonate reabsorption, acid-base balance, intracellular pH, miRNA expression profiling, essential hypertension, sodium reabsorption
- MeSH terms
- Sodium-Hydrogen Exchanger 1, Sodium-Hydrogen Exchanger 3, Essential Hypertension, Animals, Bicarbonates, Humans, Hypertension, Kidney Medulla, Sodium, Sodium Chloride, Dietary, MicroRNAs, Rats
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