Mesalamine Inhibits Epithelial β-Catenin Activation in Chronic Ulcerative Colitis

Jeffrey B. Brown, Goo Lee, Elizabeth Managlia, Gery R. Grimm, Ramanarao Dirisina, Tatiana Goretsky, Paul Cheresh, Nichole R. Blatner, Khashayarsha Khazaie, Guang Yu Yang, Linheng Li, Terrence A. Barrett

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Background & Aims: Mesalamine is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) in which condition it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that mesalamine reduces β-catenin-associated progenitor cell activation, Akt-phosphorylated β-cateninSer552 (P-β-catenin), and colitis-induced dysplasia (CID). Methods: Effects of mesalamine on P-β-catenin staining and function were assessed by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in biopsy specimens of CUC in mild or "refractory" severe mucosal inflammation. Effects of mesalamine on epithelial proliferation and activation of Akt and β-catenin were assessed in interleukin (IL)-10-/- colitis and CID by immunohistochemistry and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon. Results: Data from IL-10-/- and human colitis samples show that mesalamine reduced Akt activation and P-β-catenin levels in the middle and upper crypt. Reductions in P-β-catenin in CUC biopsy specimens with severe inflammation suggested that mesalamine reduced P-β-catenin levels in tissue refractory to mesalamine's anti-inflammatory effects. In IL-10-/- mice, mesalamine reduced CID concordant with inhibition of crypt Akt and β-catenin signaling. Conclusions: The results are consistent with the model that mesalamine contributes to chemoprevention in CAC by reducing β-catenin signaling within intestinal progenitors.

Original languageEnglish (US)
Pages (from-to)595-605.e3
JournalGastroenterology
Volume138
Issue number2
DOIs
StatePublished - Feb 2010

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Mesalamine Inhibits Epithelial β-Catenin Activation in Chronic Ulcerative Colitis'. Together they form a unique fingerprint.

  • Cite this

    Brown, J. B., Lee, G., Managlia, E., Grimm, G. R., Dirisina, R., Goretsky, T., Cheresh, P., Blatner, N. R., Khazaie, K., Yang, G. Y., Li, L., & Barrett, T. A. (2010). Mesalamine Inhibits Epithelial β-Catenin Activation in Chronic Ulcerative Colitis. Gastroenterology, 138(2), 595-605.e3. https://doi.org/10.1053/j.gastro.2009.10.038