title: Protective role of uncoupling protein-2 against dextran sodium sulfate-induced colitis.
abstract: OBJECTIVE
  Uncoupling protein-2 (UCP-2) is a negative regulator of reactive oxygen species (ROS) production. We investigated the effect of UCP-2 on disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model, and the expression and distribution of tight junction (TJ) proteins, such as occludin, zonula-1 (ZO-1), claudin-4, and junctional adhesion molecule-1 (JAM-1).
  
  
  METHODS
  Male UCP-2(-/-) mice and wild-type littermates were divided into four groups: groups I and II, which comprised each type of mouse, were administered 2.5% DSS dissolved in drinking water to create a colitis model. The control groups (groups III and IV, which comprised each type of mouse) were given normal drinking water. Disease progression was evaluated according to colon length and the disease activity index. The distribution of TJ proteins was detected by immunohistochemical analysis.
  
  
  RESULTS
  Compared with wild-type littermates, UCP-2(-/-) mice treated with DSS developed more severe diarrhea, body weight loss (P < 0.01), significantly short colon length, and more inflammatory cell infiltration into the mucosa and submucosa. The level of malondialdehyde in colonic mucosa increased in UCP-2(-/-) mice treated with DSS compared with the wild-type littermates (P < 0.001). The distribution of the ZO-1 and JAM-1 proteins was significantly decreased in the colonic mucosa of UCP-2(-/-) mice compared with the wild-type littermates, whereas occludin and claudin-4 distribution were not different between the UCP-2(-/-) mice and wild-type littermates.
  
  
  CONCLUSIONS
  UCP-2 might reduce intestinal inflammatory response through the negative regulation of ROS, and affects the expression and distribution of TJ proteins.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. hjzhang06@163.com
authors.forename: Hongjie
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Kuai
authors.forename: Pengli
authors.initials: P
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D062506:Claudin-4; D057167:Claudins / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate; D003967:Diarrhea / Q000209:etiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism*; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000009:adverse effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071246:Uncoupling Protein 2; D015431:Weight Loss; D062826:Zonula Occludens-1 Protein
chemical_list: D015815:Cell Adhesion Molecules; D062506:Claudin-4; D057167:Claudins; C568158:Cldn4 protein, mouse; C498686:F11r protein, mouse; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; C569043:Tjp1 protein, mouse; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D062826:Zonula Occludens-1 Protein; D008315:Malondialdehyde; D016264:Dextran Sulfate