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

doi:10.1053/j.gastro.2009.10.038

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 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-catenin^Ser552 (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 language	English (US)
Pages (from-to)	595-605.e3
Journal	Gastroenterology
Volume	138
Issue number	2
DOIs	https://doi.org/10.1053/j.gastro.2009.10.038
State	Published - Feb 2010

Funding

Conflicts of interest The authors disclose the following: T.A.B. received grant support from Proctor and Gamble for this project. The remaining authors disclose no conflicts. Funding Supported by NIH grants DK54778 , DKAI061701 (to T.A.B.), and DK066161 (to J.B.B.).

ASJC Scopus subject areas

Gastroenterology
Hepatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1053/j.gastro.2009.10.038

Cite this

@article{9cf9311902e14e94b0c4d15882e5cd22,

title = "Mesalamine Inhibits Epithelial β-Catenin Activation in Chronic Ulcerative Colitis",

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.",

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

note = "Funding Information: Conflicts of interest The authors disclose the following: T.A.B. received grant support from Proctor and Gamble for this project. The remaining authors disclose no conflicts. Funding Information: Funding Supported by NIH grants DK54778 , DKAI061701 (to T.A.B.), and DK066161 (to J.B.B.). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2010",

month = feb,

doi = "10.1053/j.gastro.2009.10.038",

language = "English (US)",

volume = "138",

pages = "595--605.e3",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders",

number = "2",

}

TY - JOUR

T1 - Mesalamine Inhibits Epithelial β-Catenin Activation in Chronic Ulcerative Colitis

AU - Brown, Jeffrey B.

AU - Lee, Goo

AU - Managlia, Elizabeth

AU - Grimm, Gery R.

AU - Dirisina, Ramanarao

AU - Goretsky, Tatiana

AU - Cheresh, Paul

AU - Blatner, Nichole R.

AU - Khazaie, Khashayarsha

AU - Yang, Guang Yu

AU - Li, Linheng

AU - Barrett, Terrence A.

N1 - Funding Information: Conflicts of interest The authors disclose the following: T.A.B. received grant support from Proctor and Gamble for this project. The remaining authors disclose no conflicts. Funding Information: Funding Supported by NIH grants DK54778 , DKAI061701 (to T.A.B.), and DK066161 (to J.B.B.). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2010/2

Y1 - 2010/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=75149198407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75149198407&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2009.10.038

DO - 10.1053/j.gastro.2009.10.038

M3 - Article

C2 - 19879273

AN - SCOPUS:75149198407

SN - 0016-5085

VL - 138

SP - 595-605.e3

JO - Gastroenterology

JF - Gastroenterology

IS - 2

ER -

Mesalamine Inhibits Epithelial β-Catenin Activation in Chronic Ulcerative Colitis

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this