Research Report
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World J Gastroenterol. Nov 14, 2014; 20(42): 15736-15744
Published online Nov 14, 2014. doi: 10.3748/wjg.v20.i42.15736
Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model
Jia-Yi Ma, Run-Hua Li, Kun Huang, Gao Tan, Chen Li, Fa-Chao Zhi
Jia-Yi Ma, Run-Hua Li, Kun Huang, Gao Tan, Chen Li, Fa-Chao Zhi, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: Ma JY designed and carried out the studies and drafted the manuscript; Li RH, Tan G and Li C performed the sample analyses and helped with acquisition of data; Huang K performed the statistical analysis and revised the manuscript; Zhi FC assisted in designing the study, coordination and critically reviewed the manuscript.
Supported by National Natural Science Foundation of China, No. 81170341
Correspondence to: Fa-Chao Zhi, MD, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Road, Guangzhou 510515, Guangdong Province, China.
Telephone: +86-20-61641532 Fax: +86-20-87280770
Received: March 27, 2014
Revised: June 10, 2014
Accepted: July 22, 2014
Published online: November 14, 2014

AIM: To investigate the possible role of chitinase 3-like-1 (CHI3L1) in the progression of colitis-associated carcinoma (CAC).

METHODS: Thirty-four Balb/c mice were randomly assigned to five groups, including the control, CAC control, CAC + caffeine, colitis control and colitis + caffeine. Three animals were sacrificed every two weeks for blinded macroscopic inspection, histological analysis, and total RNA extraction. An immunofluorescent assay was performed using specimens from the colitis control and colitis + caffeine groups to investigate whether the protective effect of caffeine was associated with less oxidative DNA damage. In vitro, HT29 cells pre-stimulated with different concentrations of recombinant CHI3L1 protein and H2O2 were loaded with the DCFH-DA fluorescent probe to determine the effect of CHI3L1 on intracellular reactive oxygen species production.

RESULTS: CHI3L1 mRNA was increased during the progression of colon carcinogenesis. Tumors were mostly located in the distal end of the colon where the expression of CHI3L1 was higher than in the proximal colon. Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice. CHI3L1 protein increased reactive oxygen species in HT29 cells when exposed to H2O2.

CONCLUSION: Caffeine reduces tumor incidence by decreasing oxidative DNA damage. CHI3L1 may contribute to CAC by increasing reactive oxygen species production.

Keywords: Inflammatory bowel disease, Ulcerative colitis, Colitis-associated carcinoma, Murine model, Chitinase 3-like-1, Oxidative stress, Colorectal cancer

Core tip: Increased expression of chitinase 3-like-1 (CHI3L1) mRNA was found in ulcerative colitis patients with dysplasia. It is not known whether CHI3L1 contributes to inflammation-driven carcinogenesis. Our study showed increased expression of CHI3L1 during the progression of carcinogenesis. Caffeine protected against severe inflammation and neoplasms by acting as a scavenger of reactive oxygen species (ROS), which may be partly attributed to CHI3L1 inhibition. In vitro data showed that CHI3L1 increased ROS production in colonic epithelial cells under conditions of oxidative stress. Our study has made a modest advance in the exploration of CHI3L1 in colitis-associated carcinoma.