title: Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium-induced colitis mouse model.
abstract: Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association.
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Koyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ooi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D003106:Colon / Q000473:pathology / Q000503:physiopathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008407:Mast Cells; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000097:blood; D009929:Organ Size; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D014870:Water Loss, Insensible; D015431:Weight Loss
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D009566:Nitrates; D011976:Receptors, Muscarinic; D014409:Tumor Necrosis Factor-alpha; D018738:Hexamethonium; D001285:Atropine; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D009585:Nitrogen Dioxide
keywords: acetylcholine receptor; colitis; mast cell; skin hydration; transepidermal water loss