Changes in Gene Expression Patterns of Circadian-Clock, Transient Receptor Potential Vanilloid-1 and Nerve Growth Factor in Inflamed Human Esophagus

Abstract

Circadian rhythm is driven by the molecular circadian-clock system and regulates many physiological functions. Diurnal rhythms in the gastrointestinal tract are known to be related to feeding pattern, but whether these rhythms are also related to the gastrointestinal damage or injuries; for example, gastroesophageal reflux disease (GERD), is unclear. This study was conducted to determine whether expression of circadian-clock genes or factors involved in vagal stimulation or sensitization were altered in the esophagus of GERD patients. Diurnal patterns of PER1, PER2, BMAL1, CRY2, TRPV1, and NGF mRNA expression were found in patient controls, and these patterns were altered and significantly correlated to the GERD severity in GERD patients. Although levels of CRY1, TIM, CB1, NHE3, GDNF, and TAC1 mRNA expression did not show diurnal patterns, they were elevated and also correlated with GERD severity in GERD patients. Finally, strong correlations among PER1, TRPV1, NGF and CRY2 mRNA expression, and among PER2, TRPV1 and CRY2 expression were found. Expression levels of CRY1 mRNA highly correlated with levels of TIM, CB1, NHE3, GDNF and TAC1. This study suggests that the circadian rhythm in the esophagus may be important for the mediation of and/or the response to erosive damage in GERD patients.