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Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus.

Publication ,  Journal Article
Krüger, L; Pridgen, TA; Taylor, ER; Garman, KS; Blikslager, AT
Published in: Am J Physiol Gastrointest Liver Physiol
April 1, 2020

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 ZnCl2 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.

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Published In

Am J Physiol Gastrointest Liver Physiol

DOI

EISSN

1522-1547

Publication Date

April 1, 2020

Volume

318

Issue

4

Start / End Page

G613 / G623

Location

United States

Related Subject Headings

  • Zinc Compounds
  • Time Factors
  • Swine
  • Occludin
  • Male
  • Lubiprostone
  • Hydrochloric Acid
  • Gene Expression Regulation
  • Gastroenterology & Hepatology
  • Female
 

Citation

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Krüger, L., Pridgen, T. A., Taylor, E. R., Garman, K. S., & Blikslager, A. T. (2020). Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus. Am J Physiol Gastrointest Liver Physiol, 318(4), G613–G623. https://doi.org/10.1152/ajpgi.00086.2019
Krüger, Leandi, Tiffany A. Pridgen, Ellie R. Taylor, Katherine S. Garman, and Anthony T. Blikslager. “Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus.Am J Physiol Gastrointest Liver Physiol 318, no. 4 (April 1, 2020): G613–23. https://doi.org/10.1152/ajpgi.00086.2019.
Krüger L, Pridgen TA, Taylor ER, Garman KS, Blikslager AT. Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus. Am J Physiol Gastrointest Liver Physiol. 2020 Apr 1;318(4):G613–23.
Krüger, Leandi, et al. “Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus.Am J Physiol Gastrointest Liver Physiol, vol. 318, no. 4, Apr. 2020, pp. G613–23. Pubmed, doi:10.1152/ajpgi.00086.2019.
Krüger L, Pridgen TA, Taylor ER, Garman KS, Blikslager AT. Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus. Am J Physiol Gastrointest Liver Physiol. 2020 Apr 1;318(4):G613–G623.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

EISSN

1522-1547

Publication Date

April 1, 2020

Volume

318

Issue

4

Start / End Page

G613 / G623

Location

United States

Related Subject Headings

  • Zinc Compounds
  • Time Factors
  • Swine
  • Occludin
  • Male
  • Lubiprostone
  • Hydrochloric Acid
  • Gene Expression Regulation
  • Gastroenterology & Hepatology
  • Female