Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran sulfate sodium-induced colitis.
Ulcerative colitis (UC) is a representative clinical manifestation of inflammatory bowel disease that causes chronic gastrointestinal tract inflammation. Dextran sulfate sodium (DSS)-induced colitis mice have been used to investigate UC pathogenesis, and in this UC model, disturbance and impairment of the mucosal epithelium have been reported to cause colitis. However, how DSS sporadically breaks down the epithelium remains unclear. In this study, we focused on the colonic microcirculation and myenteric neurons of DSS-induced colitis. Moreover, we examined the potential of myenteric neurons as a target to prevent exacerbation of colitis. Fluorescent angiographic and histopathological studies revealed that DSS administration elicited blood vessel disruption before epithelial disorders appeared. Ischemic conditions in the lamina propria induced inducible nitric oxide synthase (iNOS) expression in myenteric neurons as colitis aggravated. When neuronal activity was inhibited with butylscopolamine, neuronal iNOS expression decreased, and the exacerbation of colitis was prevented. These results suggested that DSS-induced colitis was triggered by microcirculatory disturbance in the mucosa, and that excessive neuronal excitation aggravated colitis. During remission periods of human UC, endoscopic inspection of the colonic microcirculation may enable the early detection of disease recurrence, and inhibition of neuronal iNOS expression may prevent the disease from worsening.
1] Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan [2] Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Hiroki
H
Saijo
Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.
Norifumi
N
Tatsumi
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Seiji
S
Arihiro
Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan.
Tomohiro
T
Kato
Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.
Masataka
M
Okabe
1] Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan [2] Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan.
Hisao
H
Tajiri
Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.
Hisashi
H
Hashimoto
D000199:Actins / Q000378:metabolism; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002086:Butylscopolammonium Bromide; D002196:Capillaries / Q000473:pathology; D002199:Capillary Permeability; D003092:Colitis / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000098:blood supply* / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D064531:Peripherins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000199:Actins; D061067:Antibodies, Monoclonal, Humanized; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064531:Peripherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; C467480:vascular endothelial growth factor A, mouse; D000068258:Bevacizumab; D002086:Butylscopolammonium Bromide; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse