Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients
| Autor: | Yuka Ikenoue, Hiroto Miwa, Takayuki Matsumoto, Takashi Ohama, Masahiko Fujisawa, Yoshio Jinno, Hiroshi Ozaki, Masatoshi Hori, Masaharu Kiyosue, Takahisa Murata, Masaki Hashimoto |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Myosin light-chain kinase Colon Blotting Western Down-Regulation Muscle Proteins Biology Proinflammatory cytokine Mice Downregulation and upregulation Internal medicine medicine Phosphoprotein Phosphatases Animals Humans Colitis Mice Knockout Mice Inbred BALB C Gastroenterology Intracellular Signaling Peptides and Proteins Interleukin Muscle Smooth medicine.disease Phosphoproteins Mice Inbred C57BL Interleukin 10 Disease Models Animal Endocrinology Muscle Tonus Knockout mouse Phosphorylation Colitis Ulcerative Electrophoresis Polyacrylamide Gel Gastrointestinal Motility |
| Zdroj: | Journal of gastroenterology. 43(11) |
| ISSN: | 0944-1174 |
| Popis: | Chronic intestinal inflammation is frequently accompanied by motility disorders. We previously reported that proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin (IL)-1beta 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. |
| Databáze: | OpenAIRE |
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