News Release

What's the influence of laxative agents on mucosal barrier repair?

Peer-Reviewed Publication

World Journal of Gastroenterology

The prostone lubiprostone has been shown to stimulate chloride secretion via one of the minor intestinal epithelial channels, ClC-2. This results in sustained low-level secretion of water into the lumen. Previous studies by the same research group have identified ClC-2 as a key protein involved in re-assembly of interepithelial tight junctions. Activation of ClC-2 by lubiprostone hastens recovery of barrier function, apparently by recruiting tight junction proteins to the apical-lateral membrane. Alternate treatments for constipation, such as PEG 3350, generate an osmotic gradient within the lumen that drags electrolytes and fluid into the lumen. Osmotic agents have also been shown to enhance barrier function by alteration of tight junction structure. However, the ability of PEG 3350 to enhance recovery of acutely injured mucosa as compared to lubiprostone has not been previously assessed.

A research article to be published on October 21, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Moeser and Blikslager at North Carolina State University in collaboration with investigators at Sucampo Inc. used electrophysiological techniques to study ischemic-injured mucosa ex vivo. Electrical responses were further assessed using mucosal-to-serosal fluxes of radiolabeled paracellular probes and tissues were examined histologically.

Ischemic-injured mucosa treated with either lubiprostone or PEG 3350 showed sharp elevations in short-circuit current, most likely associated with movement of chloride toward the luminal side of the tissue. Chloride secretion has previously been shown to be an important signal for subsequent re-assembly of tight junctions and closure of paracellular spaces within the epithelium. However, only lubiprostone stimulated rapid recovery of barrier function as detected by marked elevations in transepithelial electrical resistance and confirmed by measurement of macromolecular fluxes. Injured tissues had all restituted to the same degree, indicating that changes in barrier function were likely attributable to conformational change of the tight junction and paracellular spaces.

These results demonstrate potential therapeutic properties of the prostones beyond the current indications. Rapid recovery of barrier function has previously been shown to be linked to selective activation of ClC-2, and may lead to novel treatments of intestinal conditions characterized by periodic reductions in barrier function. A greater understanding of the signaling pathways used by prostones to initiate intestinal barrier repair may refine authors' ability to develop targeted treatments for intestinal disease.

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Reference: Moeser AJ, Nighot PK, Roerig B, Ueno R, Blikslager AT. Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine. World J Gastroenterol 2008; 14(39): 6012-6017 http://www.wjgnet.com/1007-9327/14/6012.asp

Correspondence to: Dr. Anthony T Blikslager, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh NC 27606, United States. Anthony_Blikslager@ncsu.edu Telephone: +1- 919-5137725 Fax: +1-919-5156336

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection. It provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the title China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

About The WJG Press

The WJG Press mainly publishes World Journal of Gastroenterology.


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