Papers

11 2008

Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients

JOURNAL OF GASTROENTEROLOGY
  • Takashi Ohama
  • ,
  • Masatoshi Hori
  • ,
  • Masahiko Fujisawa
  • ,
  • Masaharu Kiyosue
  • ,
  • Masaki Hashimoto
  • ,
  • Yuka Ikenoue
  • ,
  • Yoshio Jinno
  • ,
  • Hiroto Miwa
  • ,
  • Takayuki Matsumoto
  • ,
  • Takahisa Murata
  • ,
  • Hiroshi Ozaki

Volume
43
Number
11
First page
858
Last page
865
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1007/s00535-008-2241-2
Publisher
SPRINGER TOKYO

Chronic intestinal inflammation is frequently accompanied by motility disorders. We previously reported that proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin (IL)-1 beta downregulate CPI-17, an endogenous inhibitor of serine/threonine protein phosphatase in smooth-muscle cells, which results in the inhibition of myosin light chain phosphorylation and contractility. However, its clinical relevance has not been clarified.
The present study examined the changes in CPI-17 expression in chronic intestinal inflammation using smooth-muscle tissues from IL-10 knockout mice and from patients with ulcerative colitis (UC).
The IL-10 knockout mice developed spontaneous and chronic colitis accompanied by immune cell infiltration, submucosal fibrosis, and thickening of the muscularis externa. The expression of alpha-smooth muscle actin protein in the smooth-muscle layer did not change, whereas that of CPI-17 protein was decreased by about 40% compared with healthy wild-type controls. Consistent with this observation, smooth-muscle contractile force and myosin light chain phosphorylation induced by a muscarinic agonist were reduced in the knockout mice. Moreover, we observed that CPI-17 protein expression was decreased in smooth-muscle tissues from patients with UC compared with controls.
CPI-17 downregulation might contribute to the decreased motor function in chronic inflammatory bowel diseases.

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Link information
DOI
https://doi.org/10.1007/s00535-008-2241-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19012039
Scopus
https://www.scopus.com/record/display.uri?eid=2-s2.0-56649107785&origin=inward
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000261018100006&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=56649107785&origin=inward

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