Evidence for Up-Regulation of Purinergic Receptor Genes Associating with TRPV1 Receptors and Neurotrophic Factors in the Inflamed Human Esophagus

Title:Evidence for Up-Regulation of Purinergic Receptor Genes Associating with TRPV1 Receptors and Neurotrophic Factors in the Inflamed Human Esophagus

Volume: 14 Issue: 9

Author(s): K.-R. Shieh, S.-C. Yang, H.-L. Tseng, C.-H. Yi, T.-T. Liu and C.-L. Chen

Affiliation:

Keywords: Acid reflux, esophagitis, neurotrophic factors, purinergic receptors, transient receptor potential vanilloid receptors.

Abstract: Purinergic receptors are implicated in nociceptive signaling in small primary afferents via activation of adenosine triphosphate (ATP). ATP appears to mediate HCl-induced transient receptor potential vanilloid receptor 1 (TRPV1) activation in esophageal mucosa. Up-regulation of TRPV1 expression in gastroesophageal reflux disease (GERD) is associated with increased nerve growth factor (NGF) and glial derived neurotrophic factor (GDNF). This study aims to genetically determine the expression of purinergic receptors in severe inflamed human esophagus. Distal esophageal biopsies from the subjects with erosive GERD, asymptomatic patients (AP) and healthy ones were examined. Using real-time qPCR for detecting purinergic receptors (P2X₂, P2X₃, P2X₇, P2Y₁, P2Y₂, P2Y₄, P2Y₆ and P2Y₁₂), TRPV1, TRPV4, NGF, and GDNF was done in this study. Both P2X₃ and P2X₇ mRNA expressions in GERD patients significantly increased than those in healthy controls (P < 0.001) and AP (P < 0.001), but P2X₂, P2Y₁, P2Y₂, P2Y₄, P2Y₆, P2Y₁₂ or P2Y₁₂ had no difference within the control, AP or GERD subjects. The well correlated expression in P2X₃ gene with TRPV1 (r = 0.46, P = 0.002), NGF (r = 0.54, P = 0.0002), and GDNF (r = 0.64, P = 0.0001) was found. The P2X₇ gene expressions also well correlated with TRPV1 (r = 0.47, P = 0.002), NGF (r = 0.32, P = 0.037), and GDNF (r = 0.42, P = 0.005). These results suggest that chronic esophagitis increases mRNA expressions of P2X₃ and P2X₇ receptors accompanied by up-regulation of TRPV1 and neurotrophic factors (NGF and GDNF). These genetical alterations in esophageal mucosa might mediate sensitization of inflamed human esophagus.

Cite this article as:

Shieh K.-R., Yang S.-C., Tseng H.-L., Yi C.-H., Liu T.-T. and Chen C.-L., Evidence for Up-Regulation of Purinergic Receptor Genes Associating with TRPV1 Receptors and Neurotrophic Factors in the Inflamed Human Esophagus, Current Molecular Medicine 2014; 14 (9) . https://dx.doi.org/10.2174/1566524014666141021145419