Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8260397 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2014 | 11 Pages |
Abstract
In this study, we demonstrate that activation of M1 muscarinic acetylcholine receptor (mAChR) augments the restitution of epithelial barrier function in T84 cell monolayers after ethanol-induced epithelial injury, via ERK-dependent phosphorylation of focal adhesion kinase (FAK). We have shown that ethanol injury decreased the transepithelial electrical resistance (TER) along with the reduction of ERK and FAK phosphorylation. Carbachol (CCh) increased ERK and FAK phosphorylation with enhanced TER recovery, which was completely blocked by either MT-7 (M1 antagonist) or atropine. The CCh-induced enhancement of TER recovery was also blocked by either U0126 (ERK pathway inhibitor) or PF-228 (FAK inhibitor). Treatment of T84 cell monolayers with interferon-γ (IFN-γ) impaired the barrier function with the reduction of FAK phosphorylation. The CCh-induced ERK and FAK phosphorylation were also attenuated by the IFN-γ treatment. Immunological and binding experiments exhibited a significant reduction of M1 mAChR after IFN-γ treatment. The reduction of M1 mAChR in inflammatory area was also observed in surgical specimens from IBD patients, using immunohistochemical analysis. These findings provide important clues regarding mechanisms by which M1 mAChR participates in the maintenance of intestinal barrier function under not only physiological but also pathological conditions.
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Authors
Md Rafiqul Islam Khan, Takashi Yazawa, Abu Syed Md Anisuzzaman, Shingo Semba, Yanju Ma, Junsuke Uwada, Hisayoshi Hayashi, Yuichi Suzuki, Hiroki Ikeuchi, Motoi Uchino, Atsuo Maemoto, Ikunobu Muramatsu, Takanobu Taniguchi,