Mucus and adiponectin deficiency: role in chronic inflammation-induced colon cancer.

Abstract

PURPOSE:

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.

CONCLUSION:

APN may be involved in reducing the severity of CICC by preventing goblet cell apoptosis and increasing epithelial to goblet cell differentiation.

• Authors: Arpit Saxena, Manjeshwar Shrinath Baliga, Venkatesh Ponemone, Kamaljeet Kaur, Bianca Larsen, Emma Fletcher, Jennifer Greene, Raja Fayad
• Journal: International journal of colorectal disease (Int J Colorectal Dis) Vol. 28 Issue 9 Pg. 1267-79 (Sep 2013) ISSN: 1432-1262 [Electronic] Germany
• PMID: 23474825 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adiponectin
• Atoh1 protein, mouse
• Basic Helix-Loop-Helix Transcription Factors
• Receptors, Adiponectin
• Tumor Necrosis Factor-alpha
• bcl-2-Associated X Protein

Topics

• Adiponectin (deficiency, metabolism)
• Animals
• Apoptosis (drug effects)
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Carcinogenesis (drug effects, pathology)
• Cell Differentiation (drug effects, genetics)
• Cell Line, Tumor
• Chronic Disease
• Colonic Neoplasms (etiology, pathology)
• Epithelial Cells (drug effects, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Goblet Cells (drug effects, metabolism, pathology)
• Humans
• Inflammation (complications, pathology)
• Intestinal Mucosa (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Biological
• Mucus (drug effects, metabolism)
• Receptors, Adiponectin (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)
• bcl-2-Associated X Protein (metabolism)