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.
Highlights
gastroesophageal reflux disease (GERD) symptoms has been determined to act through the activation of proton-gated and acid-sensing ion channels, such as the transient receptor potential vanilloid receptor 1 (TRPV1)[7,8]
The changes of the circadian-clock system are found in breast, gastric and colorectal cancers[27,28,29], few reports have investigated whether the circadian-clock system is related to the symptoms of gastrointestinal disorders, especially GERD
Overexpression of a cell cycle-related protein (p53) has been reported in GERD patients[6], and the circadian-clock system is involved in the gating of the cell cycle[34]
Summary
GERD symptoms has been determined to act through the activation of proton-gated and acid-sensing ion channels, such as the transient receptor potential vanilloid receptor 1 (TRPV1)[7,8]. Whether the levels of CB1, CB2, NHE1, NHE3, TRPV1, NGF, GDNF and TAC1 gene expressions in GERD patients were altered and correlated to the severity of GERD symptoms was examined in this study. The mammalian circadian rhythm is driven by the molecular circadian-clock system, including the Per[1] (period 1), Per[2], Per[3], Cry[1] (cryptochrome 1), Cry[2], Bmal[1] (brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein-1), Clock (circadian locomotor output cycles kaput) and Timeless (Tim)[21,22] This molecular circadian-clock system exists throughout the whole body, including the central circadian pacemaker, the suprachiasmatic nucleus, and many peripheral tissues, such as the heart, kidney, liver and gastrointestinal tract[23,24,25,26]. This study aimed to determine whether the gene expression levels of circadian-clock genes and several factors involved in vagal stimulation or sensitization were altered by the severity in inflamed human esophagus
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