Pathophysiology of hepatic Na+/H+ exchange (Review)
Open accessAbstract
Na+/H+ exchangers (NHEs) are a family of membrane proteins that contribute to exchanging one intracellular proton for one extracellular sodium. The family of NHEs consists of nine known members, NHE1‑9. Each isoform represents a different gene product that has unique tissue expression, membrane localization, physiological effects, pathological regulation and sensitivity to drug inhibitors. NHE1 was the first to be discovered and is often referred to as the ‘housekeeping’ isoform of the NHE family. NHEs are not only involved in a variety of physiological processes, including the control of transepithelial Na+ absorption, intracellular pH, cell volume, cell proliferation, migration and apoptosis, but also modulate complex pathological events. Currently, the vast majority of review articles have focused on the role of members of the NHE family in inflammatory bowel disease, intestinal infectious diarrhea and digestive system tumorigenesis, but only a few reviews have discussed the role of NHEs in liver disease. Therefore, the present review described the basic biology of NHEs and highlighted their physiological and pathological effects in the liver.
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Intracellular alkalinization mediated by the sodium hydrogen exchanger is a permissive signal for DNA synthesis and mitotic activity.
“In fact, the intracellular alkalinization mediated by sodium hydrogen exchanger has been identified as a permissive signal for DNA synthesis and mitotic activity[78].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [78]
Section 3, “NHEs in hepatic physiological regulation” (page unavailable), says that NHE activation promotes hepatocyte proliferation and that EGF stimulates NHEs before DNA synthesis increases. It describes NHE1-mediated intracellular alkalinization as a possible antiapoptotic signal, but does not identify that alkalinization as a permissive signal for DNA synthesis or mitotic activity. (LLM, conf=0.83)
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Flagged first, then by citations
3 of the 155 references couldn’t be matched to a known paper.
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Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value
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Na+/H+ Exchanger 1, a Potential Therapeutic Drug Target for Cardiac Hypertrophy and Heart Failure
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Sodium Ions as Regulators of Transcription in Mammalian Cells
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Prolonged NHE Activation may be both Cause and Outcome of Cytokine Release Syndrome in COVID-19
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- Authors
- Li, T., & Tuo, B.
- Affiliations
- Zunyi Medical University (CN)
- Venue
- Experimental and Therapeutic Medicine
- Publisher
- Spandidos Publications
- Published
- 2020-06-12
- Volume
- 20
- Issue
- 2
- Pages
- 1220-1229
- ISSN
- 1792-0981 (ISSN-L)
- 1792-1015
- PMC
- PMC7388279
- OpenAlex
- W3035089602
- Cited by
- 17
- References
- 155
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 2 · 2020: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Experimental and Therapeutic Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- Na+/H+ exchanger, NHE1, NHE2, NHE3, NHE6, NHE8, NHE9, liver disease, intracellular pH regulation, cell volume regulation
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