2. Academic Validation
  3. Microsomal Prostaglandin E Synthase-1 Plays a Critical Role in Long-term Motility Dysfunction after Bowel Obstruction

Microsomal Prostaglandin E Synthase-1 Plays a Critical Role in Long-term Motility Dysfunction after Bowel Obstruction

  • Sci Rep. 2018 Jun 11;8(1):8831. doi: 10.1038/s41598-018-27230-6.
You-Min Lin 1,  Yu Fu 1,  Shrilakshmi Hegde 1,  Yanbo Tang 1 2,  Ravi Radhakrishnan 3,  Xuan-Zheng Shi 4
Affiliations

Affiliations

  • 1 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
  • 2 Department of Gastroenterology, The first Affiliated Hospital, Guangxi University of Science and Technology, Liuzhou, Guangxi, China.
  • 3 Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
  • 4 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. [email protected].
PMID: 29891860 DOI: 10.1038/s41598-018-27230-6
Abstract

Motility dysfunction is present not only during bowel obstruction (BO), but after obstruction is resolved. Previous studies found that lumen distension associated mechano-transcription of COX-2 and production of PGE2 in gut smooth muscle cells (SMC) account for motility dysfunction during obstruction. We hypothesized that PGE2 may exert autocrine effect in SMC to induce microsomal prostaglandin E synthase-1 (mPGES-1), which contributes to motility dysfunction after obstruction is resolved. Partial colon obstruction was induced in rats with an obstruction band, which was released 7 days later. Rats were further studied in the post-BO state. Circular muscle contractility of the mid colon (previously distended during obstruction) remained suppressed, and colon transit was impaired in the post-BO state. The COX-2, mPGES-1, and PGE2 levels were all increased in the distended bowel during obstruction. However, after obstruction was resolved, COX-2 expression returned to normal, whereas mPGES-1 and PGE2 levels remained increased. Expression of mPGES-1 in colon SMC was inducible by stretch or PGE2. Administration of mPGES-1 inhibitor Cay 10526 either before or after the release of obstruction normalized PGE2 levels and improved motility in the post-BO rats. In conclusion, mPGES-1 plays a critical role in the continuous suppression of motor function in the post-BO state.

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