EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus

Eun Jung Jun, Jung Hoon Park, Jiaywei Tsauo, Su Geun Yang, Dae Kee Kim, Kun Yung Kim, Min Tae Kim, Sung Hwan Yoon, Young Je Lim, Ho Young Song

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background and Aims Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. Methods Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. Results SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-β1 and increased the expression level of E-cadherin (all P < .01). Conclusions EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.

Original languageEnglish (US)
Pages (from-to)219-228
Number of pages10
JournalGastrointestinal Endoscopy
Volume86
Issue number1
DOIs
StatePublished - Jul 2017
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Gastroenterology

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    Jun, E. J., Park, J. H., Tsauo, J., Yang, S. G., Kim, D. K., Kim, K. Y., Kim, M. T., Yoon, S. H., Lim, Y. J., & Song, H. Y. (2017). EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus. Gastrointestinal Endoscopy, 86(1), 219-228. https://doi.org/10.1016/j.gie.2017.01.013