ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
LPA stimulates intestinal DRA gene transcription via LPA2 receptor, PI3K/AKT, and c-Fos-dependent pathway.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Up-regulation of SLC26A3 enhances oxaliplatin sensitivity in colorectal cancer.Discover oncology · 2026Article
- High-Fat Diet-Induced Obesity Enhances Small Intestinal Glucose and NaCl Absorption Through Selective Transporter Reprogramming.International journal of molecular sciences · 2026Article
- Dexamethasone Upregulates the Expression of the Human SLC26A3 (DRA, Down-Regulated in Adenoma) Transporter (an IBD Susceptibility Gene) in Intestinal Epithelial Cells and Attenuates Gut Inflammation.Inflammatory bowel diseases · 2025Article
- SLC26A3/NHERF2-IκB/NFκB/p65 feedback loop suppresses tumorigenesis and metastasis in colorectal cancer.Oncogenesis · 2023Article
- SLC26A3 (DRA) is stimulated in a synergistic, intracellular CaAmerican journal of physiology. Cell physiology · 2023Article
- Is intestinal transport dysfunctional in COVID-19-related diarrhea?American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Alteration of Cellular Energy Metabolism through LPAR2-Axin2 Axis in Gastric Cancer.Biomolecules · 2022Article
- Article
- Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach.Frontiers in pharmacology · 2020Article
- Lysophosphatidic acid induces the migration and invasion of SGC-7901 gastric cancer cells through the LPA2 and Notch signaling pathways.International journal of molecular medicine · 2019Article
- The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018Review
- Transcriptional modulation of SLC26A3 (DRA) by sphingosine-1-phosphate.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- All-trans-retinoic Acid Increases SLC26A3 DRA (Down-regulated in Adenoma) Expression in Intestinal Epithelial Cells via HNF-1β.The Journal of biological chemistry · 2015Article
- Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells.American journal of physiology. Cell physiology · 2014Article
- Orally administered phosphatidic acids and lysophosphatidic acids ameliorate aspirin-induced stomach mucosal injury in mice.Digestive diseases and sciences · 2013Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
DRA (downregulated in adenoma) or SLC26A3 is the major apical anion exchanger mediating Cl(-) absorption in intestinal epithelial cells. Disturbances in DRA function and expression have been implicated in diarrheal conditions such as congenital chloride diarrhea and inflammatory bowel diseases. Previous studies have shown that DRA is subject to regulation by short-term and transcriptional mechanisms. In this regard, we have recently shown that short-term treatment by lysophosphatidic acid (LPA), an important bioactive phospholipid, stimulates Cl(-)/HCO(3)(-)(OH(-)) exchange activity via an increase in DRA surface levels in human intestinal epithelial cells. However, the long-term effects of LPA on DRA at the level of gene transcription have not been examined. The present studies were aimed at investigating the effects of LPA on DRA function and expression as well as elucidating the mechanisms underlying its transcriptional regulation. Long-term LPA treatment increased the Cl(-)/HCO(3)(-) exchange activity in Caco-2 cells. LPA treatment (50-100 μM) of Caco-2 cells significantly stimulated DRA mRNA levels and DRA promoter activity (-1183/+114). This increase in DRA promoter activity involved the LPA2 receptor and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. Progressive deletions from -1183/+114 to -790/+114 abrogated the stimulatory effects of LPA, indicating that the -1183/-790 promoter region harbors LPA response elements. Utilizing EMSA and mutational studies, our results showed that LPA induced the DRA promoter activity in a c-Fos-dependent manner. LPA also increased the protein expression of c-Fos and c-Jun in Caco-2 cells. Furthermore, overexpression of c-Fos but not c-Jun enhanced the DRA promoter activity. This increase in DRA transcription in response to LPA indicates that LPA may act as an antidiarrheal agent and could be exploited for the treatment of diarrhea associated with inflammatory or infectious diseases of the gut.
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