Regulation of nutrient and electrolyte absorption in human organoid-derived intestinal epithelial cell monolayers
Open accessAbstract
Recently developed human intestinal epithelial 3D organoid cultures are a useful cell culture model to study intestinal transport physiology. From these, 2D monolayer cultures can be generated in which apical transporters are exposed to the medium, thereby better facilitating in vitro investigation of intestinal absorption processes. However, whether nutrient and electrolyte absorption can be physiologically regulated in human organoid-derived monolayers has not been determined. Constitutive nitric oxide (cNO) is known to regulate multiple gastrointestinal physiological functions. Previous studies using in vivo and in vitro mammalian animal models indicate that enhanced intracellular cNO differentially regulates the two primary apical Na transporters in small intestinal epithelial cells. Here, we generated human jejunal organoid-derived monolayers to determine whether apical nutrient and electrolyte transporter function is regulated by cNO in human enterocytes. Western blot analysis and immunocytochemical staining showed that organoid-derived 2D cultures express markers of enterocyte differentiation and form intact monolayers of apical-basal polarized epithelial cells. Uptake studies demonstrated that jejunal monolayers exhibit functional activity of Na-glucose cotransporter 1 (SGLT1; SLC5A1) and Na-H exchanger 3 (NHE3; SLC9A3). In response to physiological increases in cNO, the two primary apical Na transporters were differentially regulated in human intestinal organoid-deri…
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Enhanced intracellular cNO inhibits NHE3 but stimulates SGLT1 in differentiated human jejunal organoid-derived monolayers.
“Consistent with our previous studies performed in mammalian intestinal epithelial cell models [25], we recently showed that enhanced intracellular cNO inhibits NHE3 but stimulates SGLT1 in differentiated human jejunal organoid-derived monolayers [18].”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [18]
The integrity and apical-basal polarity of intestinal epithelial cell monolayers was demonstrated by immunostaining for the tight junction protein ZO-1.
“The integrity and apical–basal polarity of intestinal epithelial cell monolayers was demonstrated by immunostaining for the tight junction protein ZO-1 (Figure 1D) [18]”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [18]
Recent work from the authors' laboratory demonstrated that human jejunal organoid monolayers can be used as an in vitro model to investigate the regulation of nutrient and electrolyte absorption.
“Moreover, recent work from our laboratory demonstrated that human jejunal organoid monolayers can be used as an in vitro model to investigate the regulation of nutrient and electrolyte absorption [18].”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [18]
Jejunal organoid monolayers are an ideal in vitro model to investigate the regulation of apical transporter function in human enterocytes.
“Along with our previous study [18], here we demonstrate that jejunal organoid monolayers are an ideal in vitro model to investigate the regulation of apical transporter function in human enterocytes.”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [18]
cNO, acting through cGMP/PKG signaling, inhibits NHE3 but stimulates SGLT1 in human jejunal organoid monolayers across multiple human specimens.
“Consistent with our previous studies, we recently demonstrated that cNO, which mediates its effects through cGMP/PKG signaling, also inhibits NHE3 but stimulates SGLT1 in human jejunal organoid monolayers, across multiple human specimens [18].”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [18]
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Replication of human noroviruses in stem cell–derived human enteroids
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Physiology of Intestinal Absorption and Secretion
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Haynes, J., Palaniappan, B., Crutchley, J. M., & Sundaram, U. (2024) · Cells · doi:10.3390/cells13191623 · Cited by 2 · see citing works
“Previously established jejunal organoids were cultured in 3D as described (organoid model MU-007) [18].”
BackgroundMethodResultInfluentialSelf-citation
- Authors
- Haynes, J., Palaniappan, B., Tsopmegha, E., & Sundaram, U.
- Affiliations
- Marshall University (US)
- Corresponding author
- Sundaram, Uma
- Venue
- Translational Research
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 248
- Pages
- 22-35
- ISSN
- 1878-1810 (ISSN-L)
- 1931-5244
- OpenAlex
- W4225281061
- Cited by
- 11
- References
- 4
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 2 · 2022: 1
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 329 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Translational research (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK-108054, DK-67420, P20GM121299-01A1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- nitric oxide, intestinal nutrient absorption, electrolyte uptake, SGLT1, NHE3, enterocyte differentiation, human intestinal epithelium, in vitro intestinal model, Na+/glucose cotransport, Na+/H+ exchanger
- MeSH terms
- Sodium-Hydrogen Exchanger 3, Nutrients, Animals, Electrolytes, Epithelial Cells, Humans, Intestinal Mucosa, Nitric Oxide, Organoids, Sodium, Sodium-Hydrogen Exchangers, Sodium-Glucose Transporter 1
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