Evidence for neurotrophic factors associating with TRPV1 gene expression in the inflamed human esophagus


Address for CorrespondenceChien-Lin Chen MD, PhD, Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien, Taiwan.
Tel: +886 3 8561825; fax: +886 3 8577161;
e-mail: harry.clchen@msa.hinet.netK.R.S. and C.H.Y. contributed equally to this manuscript and are therefore to be considered as co-first authors.


Background  Transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the mechanism of acid induced inflammation in gastro-esophageal reflux disease (GERD). It has been demonstrated that the increase in nerve growth factor (NGF) and glial derived neurotrophic factor (GDNF) was associated with the increased expression of TRPV1. We aimed to determine whether expression of TRPV1 was increased in severe inflamed human esophagus, and to test the hypothesis whether the expression of TRPV1 was mediated by neurotrophic factors such as NGF and GDNF.

Methods  We compared biopsies taken from the distal esophagus of 15 patients with erosive GERD, 16 asymptomatic patients (AP), and 10 healthy controls. We assessed the biopsies with reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative polymerase chain reaction (qPCR) for TRPV1, NGF, and GDNF. Immunohistochemical analysis of TRPV1 protein expression was also determined.

Key Results  Transient receptor potential vanilloid-1 mRNA level and its protein expression were significantly greater in patients with erosive esophagitis than AP (P < 0.001) and healthy controls (P < 0.001). Nerve growth factor and GDNF gene levels in the esophageal mucosa were also significantly increased in patients with erosive esophagitis compared with AP and healthy controls (all P < 0.001). Transient receptor potential vanilloid-1 mRNA correlated well with NGF (r = 0.61, P < 0.001) and GDNF (r = 0.58, P < 0.001).

Conclusions & Inferences  These results support the association of NGF and GDNF in the up-regulation of TRPV1 receptors in patients with erosive esophagitis.