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Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0017168 (
gastroesophageal reflux disease
)
11,783
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Esophageal injury from acid exposure related to
gastroesophageal reflux disease
is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including
ClC-2
, in the setting of acid-related esophageal injury. After finding evidence of CFTR and
ClC-2
in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the
ClC-2
agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue (
P
< 0.05). Evaluation of the interepithelial tight junctions showed well-defined membrane localization of occludin in lubiprostone-treated injured tissues. Pretreatment of tissues with the Na
+
-K
+
-2Cl
-
cotransporter inhibitor bumetanide blocked lubiprostone-induced increases in short-circuit current and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of
ClC-2
with ZnCl
2
blocked the effects of lubiprostone. We conclude that
ClC-2
contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target.
NEW & NOTEWORTHY
This research is the first to describe the presence of anion channels
ClC-2
and CFTR localized to the basal epithelia of porcine esophageal mucosa and the esophageal submucosal glands. In the setting of ex vivo acid exposure, the
ClC-2
agonist lubiprostone reduced acid-related injury and enhanced recovery of the epithelial barrier. This work may ultimately provide an alternate mechanism for treating
gastroesophageal reflux disease
.
...
PMID:Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus. 3206 40
