title: Caudal type homeobox 2 expression induced by leukocytapheresis might be associated with mucosal healing in ulcerative colitis.
abstract: OBJECTIVE
  Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. Although the goal of UC therapy has recently been to target mucosal healing, the molecular mechanism of mucosal healing remains unknown. In this study, we aimed to elucidate the molecular dynamics related to the proliferation and differentiation of intestinal epithelial cells during cytapheresis therapy in a short duration.
  
  
  METHODS
  Endoscopy was performed in 26 patients with UC in multicentre hospitals, and biopsy specimens were collected from the rectum before and within two weeks after leukocytapheresis (LCAP). The expression of representative proteins in intestinal epithelial cells and pathological findings was compared before and after LCAP.
  
  
  RESULTS
  The expression of caudal type homeobox 2 (CDX2) and a hes family bHLH transcription factor 1(HES1) markedly increased after LCAP. Patients with endoscopic improvement after LCAP showed the expression of CDX2 before LCAP. Moreover, the number of goblet cells significantly increased after LCAP. Patients without endoscopic improvement after LCAP did not show the expression of CDX2 before LCAP. However, the expression of CDX2 markedly increased after LCAP.
  
  
  CONCLUSIONS
  This study suggests that cytapheresis might induce CDX2 expression without affecting the cell proliferation, thus resulting in mucosal healing with goblet cell restoration.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.|Endoscopy and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Hibiya
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Nobukatsu
authors.initials: N
authors.lastname: Horita
authors.affiliation: Department of Pathology, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Negi
authors.affiliation: Department of Pathology, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Itoh
authors.affiliation: Department of Pathology, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Akashi
authors.affiliation: Department of Pathology, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.affiliation: IBD Center, Sapporo Kosei General Hospital, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Motoya
authors.affiliation: Department of Medicine, Division of Gastroenterology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kunisaki
authors.affiliation: Department of Inflammatory Bowel Disease, Division of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Fukunaga
authors.affiliation: Department of Inflammatory Bowel Disease, Division of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Tokyo Yamate Medical Center, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Tokyo Yamate Medical Center, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takazoe
authors.affiliation: Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Bunei
authors.initials: B
authors.lastname: Iizuka
authors.affiliation: Toho University Medical Center Sakura Hospital, Shimoshizu, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nagahori
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D000071616:CDX2 Transcription Factor / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D020397:Goblet Cells / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D012038:Regeneration / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human
keywords: Atoh1; CDX2; LCAP; mucosal healing