ArticleGastroenterology2010
Lysophosphatidic acid stimulates the intestinal brush border Na(+)/H(+) exchanger 3 and fluid absorption via LPA(5) and NHERF2.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 114 citations in OpenAlex.
- Alterations in cellular metabolic pathway and epithelial cell maturation induced by MYO5B defects are partially reversible by LPAR5 activation.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Modeling the cell biology of monogenetic intestinal epithelial disorders.The Journal of cell biology · 2024Review
- LPAAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- A dual role of lysophosphatidic acid type 2 receptor (LPAR2) in nonsteroidal anti-inflammatory drug-induced mouse enteropathy.Acta pharmacologica Sinica · 2024Article
- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
- Inhibition of protein kinase C-α and activation of ezrin byAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Emerging Roles of Lysophosphatidic Acid in Macrophages and Inflammatory Diseases.International journal of molecular sciences · 2023Review
- Comparative Analyses Reveal the Genetic Mechanism of Ambergris Production in the Sperm Whale Based on the Chromosome-Level Genome.Animals : an open access journal from MDPI · 2023Article
- Metformin Inhibits NaFrontiers in physiology · 2022Article
- Survival of Stem Cells and Progenitors in the Intestine Is Regulated by LPACellular and molecular gastroenterology and hepatology · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Article
- Luminal Chemosensory Cells in the Small Intestine.Nutrients · 2021Review
- Lysophosphatidic acid (LPA) as a modulator of plasma membrane CaJournal of physiology and biochemistry · 2021Article
- Pharmacological and Parenteral Nutrition-Based Interventions in Microvillus Inclusion Disease.Journal of clinical medicine · 2020Review
- Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Lysophosphatidic Acid Increases Maturation of Brush Borders and SGLT1 Activity in MYO5B-deficient Mice, a Model of Microvillus Inclusion Disease.Gastroenterology · 2020Article
- LPAR2 receptor activation attenuates radiation-induced disruption of apical junctional complexes and mucosal barrier dysfunction in mouse colon.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- A SNP of bacterial blc disturbs gut lysophospholipid homeostasis and induces inflammation through epithelial barrier disruption.EBioMedicine · 2020Article
- Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach.Frontiers in pharmacology · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsDiarrhea results from reduced net fluid and salt absorption caused by an imbalance in intestinal absorption and secretion. The bulk of sodium and water absorption in the intestine is mediated by Na(+)/H(+) exchanger 3 (NHE3), located in the luminal membrane of enterocytes. We investigated the effect of lysophosphatidic acid (LPA) on Na(+)/H(+) exchanger activity and Na(+)-dependent fluid absorption in the intestine.
methodsWe analyzed the effects of LPA on fluid absorption in intestines of wild-type mice and mice deficient in Na(+)/H(+) exchanger regulatory factor 2 (NHERF2; Nherf2(-/-)) or LPA(2) (Lpa(2)(-/-)). Roles of LPA(5) and NHERF2 were determined by analysis of heterologous expression.
resultsUnder basal conditions, LPA increased fluid absorption in an NHE3-dependent manner and restored the net fluid loss in a mouse model of acute diarrhea. Expression of the LPA receptor LPA(5) was necessary for LPA-induced stimulation of NHE3 activity in colonic epithelial cells. Stimulation of NHE3 by the LPA-LPA(5) signaling required coexpression of NHERF2, which interacted with LPA(5). LPA-mediated intestinal fluid absorption was impaired in Nherf2(-/-) mice, demonstrating the requirement for NHERF2 in LPA(5) activity. However, fluid absorption was unaltered in Lpa(2)(-/-) mice. LPA stimulated NHE3 and fluid absorption in part by increasing NHE3 protein abundance at the brush border membrane of intestinal epithelial cells.
conclusionsLPA is a potent stimulant of NHE3 and fluid absorption in the intestine, signaling through LPA(5). Regulation by LPA(5) depends on its interaction with NHERF2. LPA might be useful in the treatment of certain diarrheal diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.