title: Mucus and adiponectin deficiency: role in chronic inflammation-induced colon cancer.
abstract: OBJECTIVE
  This study aims to define the role of adiponectin (APN) in preventing goblet cell apoptosis and in differentiation of epithelial cells to goblet cell lineage resulting in greater mucus production and hence greater protection from chronic inflammation-induced colon cancer (CICC).
  
  
  METHODS
  Six- to eight-week-old male APNKO and C57BL/6 (WT) mice were randomly distributed to three treatment groups: DSS, DMH, DSS + DMH and control. Chronic inflammation was induced in DSS and DSS + DMH group by administrating 2 % DSS in drinking water for 5 days followed by 5 days of normal drinking water and this constitutes one DSS cycle. Three cycles of DSS were administered to induce chronic inflammation. Cancer was induced in both APNKO and WT mice in DMH and DSS + DMH groups by intraperitoneal injections of DMH (20 mg/kg body weight) once for DSS + DMH group and once per week for 12 weeks for DMH group. On day 129, the colon tissue was dissected for mucus thickness measurements and for genomic studies. HT29-C1.16E and Ls174T cells were used for several genomic and siRNA studies.
  
  
  RESULTS
  APNKO mice have more tumors and tumor area in DSS + DMH group than WT mice. APN deficiency downregulated goblet to epithelial cell ratio and enhanced the colonic mucosal erosion with reduced mucus thickness. APN increases Muc2 production with no affect on Muc1 production. APN abated goblet cell apoptosis, while APN deficiency reduced epithelial to goblet cell differentiation.
  
  
  CONCLUSIONS
  APN may be involved in reducing the severity of CICC by preventing goblet cell apoptosis and increasing epithelial to goblet cell differentiation.
authors.affiliation: Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Arpit
authors.initials: A
authors.lastname: Saxena
authors.forename: Manjeshwar Shrinath
authors.initials: MS
authors.lastname: Baliga
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Ponemone
authors.forename: Kamaljeet
authors.initials: K
authors.lastname: Kaur
authors.forename: Bianca
authors.initials: B
authors.lastname: Larsen
authors.forename: Emma
authors.initials: E
authors.lastname: Fletcher
authors.forename: Jennifer
authors.initials: J
authors.lastname: Greene
authors.forename: Raja
authors.initials: R
authors.lastname: Fayad
mesh_terms: D052242:Adiponectin / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002908:Chronic Disease; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D052242:Adiponectin; D051792:Basic Helix-Loop-Helix Proteins; D054419:Receptors, Adiponectin; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C500943:Atoh1 protein, mouse