title: Muc-2-deficient mice display a sex-specific, COX-2-related impairment of gastric mucosal repair.
abstract: Mucus is known to contribute significantly to the prevention and repair of mucosal damage throughout the gastrointestinal tract. Although not normally expressed in the stomach, mucin-2 (MUC-2, encoded by the MUC2 gene) is expressed in certain disease states. The aim of this study was to determine in a mouse model whether the absence of Muc-2 would result in impaired susceptibility to and healing of gastric mucosal injury. Acute gastric damage was induced in mice deficient in Muc-2 and in wild-type controls, through oral administration of indomethacin. Chronic gastric ulcers were induced by serosal application of acetic acid. The extent of injury and the extent of healing of the damage over time were examined in both models. Indomethacin administration caused similar levels of gastric damage in Muc-2-deficient and wild-type mice, but the erosions healed more slowly in the former. Acetic acid-induced gastric ulcers were initially similar in size in Muc-2-deficient and wild-type mice of both sexes, but ulcer healing was significantly impaired in male Muc-2-deficient mice. Induction of cyclooxygenase-2 in the stomach, in response to indomethacin- or acetic acid-induced ulceration, was significantly reduced in male Muc-2-deficient mice. This phenomenon, and the sex specificity, was also apparent in bone marrow-derived macrophages stimulated with endotoxin. These results demonstrate a marked impairment of gastric mucosal repair in male Muc-2-deficient mice that may be related to an insufficient induction of cyclooxygenase-2, an enzyme known to contribute to mucosal repair.
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. jwalla@mcmaster.ca
authors.forename: John L
authors.initials: JL
authors.lastname: Wallace
authors.forename: Linda
authors.initials: L
authors.lastname: Vong
authors.forename: Poonam
authors.initials: P
authors.lastname: Dharmani
authors.forename: Vikas
authors.initials: V
authors.lastname: Srivastava
authors.forename: Kris
authors.initials: K
authors.lastname: Chadee
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology*; D007213:Indomethacin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055271:Mucin 5AC / Q000378:metabolism; D055262:Mucin-2 / Q000172:deficiency* / Q000378:metabolism; D012727:Sex Characteristics; D013276:Stomach Ulcer / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: C524626:Muc2 protein, mouse; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D055262:Mucin-2; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D007213:Indomethacin