Lysophosphatidic Acid Increases Maturation of Brush Borders and SGLT1 Activity in MYO5B-deficient Mice, a Model of Microvillus Inclusion Disease.

Gastroenterology
Izumi KajiJames R Goldenring

Abstract

Myosin VB (MYO5B) is an essential trafficking protein for membrane recycling in gastrointestinal epithelial cells. The inactivating mutations of MYO5B cause the congenital diarrheal disease, microvillus inclusion disease (MVID). MYO5B deficiency in mice causes mislocalization of SGLT1 and NHE3, but retained apical function of CFTR, resulting in malabsorption and secretory diarrhea. Activation of lysophosphatidic acid (LPA) receptors can improve diarrhea, but the effect of LPA on MVID symptoms is unclear. We investigated whether LPA administration can reduce the epithelial deficits in MYO5B-knockout mice. Studies were conducted with tamoxifen-induced, intestine-specific knockout of MYO5B (VilCreERT2;Myo5bflox/flox) and littermate controls. Mice were given LPA, an LPAR2 agonist (GRI977143), or vehicle for 4 days after a single injection of tamoxifen. Apical SGLT1 and CFTR activities were measured in Üssing chambers. Intestinal tissues were collected, and localization of membrane transporters was evaluated by immunofluorescence analysis in tissue sections and enteroids. RNA sequencing and enrichment analysis were performed with isolated jejunal epithelial cells. Daily administration of LPA reduced villus blunting, frequency of mul...Continue Reading

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Citations

Dec 31, 2020·Journal of Clinical Medicine·Changsen LengSven C D van IJzendoorn
Feb 7, 2021·Cellular and Molecular Gastroenterology and Hepatology·Amy C EngevikJames R Goldenring
Apr 17, 2021·Mucosal Immunology·Fabienne Charbit-HenrionNadine Cerf-Bensussan
May 12, 2021·Cellular and Molecular Gastroenterology and Hepatology·Mo WangC Chris Yun
Aug 11, 2020·Gastroenterology·Shabnam Abtahi, Jerrold R Turner
Jul 2, 2021·JCI Insight·Izumi KajiJames R Goldenring

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