Brian Paul Herring1, April M Hoggatt1, Anita Gupta2, John M Wo2. 1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana. 2. Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Abstract
BACKGROUND AND AIMS: The transcription factors FOXF1 and FOXF2 have been implicated in the development of the gastrointestinal tract but their role in adults or in gastrointestinal diseases is poorly understood. We have recently shown that expression of serum response factor (SRF), a transcription factor whose activity is modulated by FOXF proteins, is decreased in the stomach muscularis of patients with gastroparesis. The aim of the current study was to determine whether FOXF expression is decreased in gastroparesis patients and whether loss of FOXF1 and/or FOXF2 from adult smooth muscle is sufficient to impair gastric emptying in mice. METHODS: Full-thickness stomach biopsy samples were collected from control subjects and from patients with gastroparesis. mRNA was isolated from the muscularis externa, and FOXF mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. Foxf1 and Foxf2 were knocked out together and separately from smooth muscle cells in adult mice, and the subsequent effect on liquid gastric emptying and contractile protein expression was determined. KEY RESULTS: Expression of FOXF1 and FOXF2 is decreased in smooth muscle tissue from gastroparesis patients. Knockout of Foxf1 and Foxf2 together, but not alone, from mouse smooth muscle resulted in delayed liquid gastric emptying. Foxf1/2 double knockout mice had decreased expression of smooth muscle contractile proteins, SRF, and myocardin in stomach muscularis. CONCLUSIONS AND INFERENCES: Our findings suggest that decreased expression of FOXF1 and FOXF2 may be contributing to the impaired gastric emptying seen in gastroparesis patients.
BACKGROUND AND AIMS: The transcription factors FOXF1 and FOXF2 have been implicated in the development of the gastrointestinal tract but their role in adults or in gastrointestinal diseases is poorly understood. We have recently shown that expression of serum response factor (SRF), a transcription factor whose activity is modulated by FOXF proteins, is decreased in the stomach muscularis of patients with gastroparesis. The aim of the current study was to determine whether FOXF expression is decreased in gastroparesispatients and whether loss of FOXF1 and/or FOXF2 from adult smooth muscle is sufficient to impair gastric emptying in mice. METHODS: Full-thickness stomach biopsy samples were collected from control subjects and from patients with gastroparesis. mRNA was isolated from the muscularis externa, and FOXF mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. Foxf1 and Foxf2 were knocked out together and separately from smooth muscle cells in adult mice, and the subsequent effect on liquid gastric emptying and contractile protein expression was determined. KEY RESULTS: Expression of FOXF1 and FOXF2 is decreased in smooth muscle tissue from gastroparesispatients. Knockout of Foxf1 and Foxf2 together, but not alone, from mouse smooth muscle resulted in delayed liquid gastric emptying. Foxf1/2 double knockout mice had decreased expression of smooth muscle contractile proteins, SRF, and myocardin in stomach muscularis. CONCLUSIONS AND INFERENCES: Our findings suggest that decreased expression of FOXF1 and FOXF2 may be contributing to the impaired gastric emptying seen in gastroparesispatients.
Authors: Blair B Madison; Lindsay B McKenna; Diane Dolson; Douglas J Epstein; Klaus H Kaestner Journal: J Biol Chem Date: 2008-12-02 Impact factor: 5.157
Authors: B P Herring; A M Hoggatt; A Gupta; S Griffith; A Nakeeb; J N Choi; M T Idrees; T Nowak; D L Morris; J M Wo Journal: Neurogastroenterol Motil Date: 2017-10-20 Impact factor: 3.598
Authors: Bhupal P Bhetwal; Changlong An; Salah A Baker; Kristin L Lyon; Brian A Perrino Journal: J Muscle Res Cell Motil Date: 2013-04-11 Impact factor: 2.698
Authors: April M Hoggatt; Ju-Ryoung Kim; Vladimir Ustiyan; Xiaomeng Ren; Tanya V Kalin; Vladimir V Kalinichenko; B Paul Herring Journal: J Biol Chem Date: 2013-08-14 Impact factor: 5.157
Authors: Mathias Mericskay; Jocelyne Blanc; Eva Tritsch; Raphael Moriez; Philippe Aubert; Michel Neunlist; Robert Feil; Zhenlin Li Journal: Gastroenterology Date: 2007-09-16 Impact factor: 22.682