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Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa
Author(s) -
Herring B. P.,
Hoggatt A. M.,
Gupta A.,
Griffith S.,
Nakeeb A.,
Choi J. N.,
Idrees M. T.,
Nowak T.,
Morris D. L.,
Wo J. M.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13230
Subject(s) - gastroparesis , interstitial cell of cajal , stomach , medicine , messenger rna , gastroenterology , immunohistochemistry , gastric emptying , pathology , endocrinology , biology , gene , biochemistry
Background The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNA s encoding proteins required for the normal motility functions of the stomach. Methods Full‐thickness stomach biopsy samples were collected from non‐diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase ( RT )‐PCR. Key Results Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNA s encoding several contractile proteins, such as MYH 11 and MYLK 1. Conversely, there was no significant change in mRNA s characteristic of interstitial cells of Cajal ( ICC s) such as KIT or ANO 1. There was also a significant decrease in mRNA ‐encoding platelet‐derived growth factor receptor α ( PDGFR α) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK 1, ANO 1 and PDGFR α showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder‐symptom severity index scores. Conclusions and Inferences: Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFR α + cells without a significant change in ICC s.