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Cited by 28Ion Transport and Channel RegulationDrug Transport and Resistance MechanismsDigestive system and related health

Reciprocal regulation of the primary sodium absorptive pathways in rat intestinal epithelial cells

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Coon, Steven, Kekuda, Ramesh, Saha, Prosenjit, Sundaram, Uma·2011·American Journal of Physiology-Cell Physiology
DOI 10.1152/ajpcell.00292.2010PMC PMC3063980
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Abstract

Sodium absorption in the mammalian small intestine occurs predominantly by two primary pathways that include Na/H exchange (NHE3) and Na-glucose cotransport (SGLT1) on the brush border membrane (BBM) of villus cells. However, whether NHE3 and SGLT1 function together to regulate intestinal sodium absorption is unknown. Nontransformed small intestinal epithelial cells (IEC-18) were transfected with either NHE3 or SGLT1 small interfering RNAs (siRNAs) and were grown in confluent monolayers on transwell plates to measure the effects on Na absorption. Uptake studies were performed as well as molecular studies to determine the effects on NHE3 and SGLT1 activity. When IEC-18 monolayers were transfected with silencing NHE3 RNA, the cells demonstrated decreased NHE3 activity as well as decreased NHE3 mRNA and protein. However, in NHE3 siRNA-transected cells, SGLT1 activity, mRNA, and protein in the BBM were significantly increased. Thus, inhibition of NHE3 expression regulates the expression and function of SGLT1 in the BBM of intestinal epithelial cells. In addition, IEC-18 cells transected with silencing SGLT1 RNA demonstrated an inhibition of Na-dependent glucose uptake and a decrease in SGLT1 activity, mRNA, and protein levels. However, in these cells, Na/H exchange activity was significantly increased. Furthermore, NHE3 mRNA and protein levels were also increased. Therefore, the inhibition of SGLT1 expression stimulates the transcription and function of NHE3 and vice versa in the BBM of intestinal epithelial cells. Thus this study demonstrates that the major sodium absorptive pathways together function to regulate sodium absorption in epithelial cells.

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Authors
Coon, S., Kekuda, R., Saha, P., & Sundaram, U.
Affiliations
West Virginia University (US)
Corresponding author
Sundaram, Uma
ORCID
Venue
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Published
2011-03
Volume
300
Issue
3
Pages
C496-C505
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
DOI
10.1152/ajpcell.00292.2010
PMC
PMC3063980
OpenAlex
W2157476765
Cited by
28
References
0
Citations by year
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FWCI
0.39
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r29dk045062-06)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-45062, R01DK058034, DK 58034)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
Keywords
intestinal sodium absorption, Na+/H+ exchange, NHE3, SGLT1, Na+/glucose cotransport, brush border membrane, reciprocal regulation, small intestinal epithelial cells, IEC-18 cells, gene silencing
MeSH terms
Sodium-Hydrogen Exchanger 3, Animals, Cell Line, Intestinal Absorption, Intestinal Mucosa, Microvilli, RNA, Messenger, Sodium, Transcription, Genetic, Signal Transduction, Down-Regulation, Sodium-Hydrogen Exchangers, Feedback, Physiological, RNA, Small Interfering, Sodium-Glucose Transporter 1, Rats, Gene Knockdown Techniques

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