Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model.
OBJECTIVE
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.


CONCLUSIONS
Caffeine reduces tumor incidence by decreasing oxidative DNA damage. CHI3L1 may contribute to CAC by increasing reactive oxygen species production.
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.
Jia-Yi
JY
Ma
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.
Run-Hua
RH
Li
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.
Kun
K
Huang
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.
Gao
G
Tan
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.
Chen
C
Li
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.
Fa-Chao
FC
Zhi
D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D000071451:Chitinase-3-Like Protein 1; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004249:DNA Damage; D016264:Dextran Sulfate; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D054392:Adipokines; D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; C084533:CHI3L1 protein, human; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D012333:RNA, Messenger; D002110:Caffeine; D016264:Dextran Sulfate; D006861:Hydrogen Peroxide
Chitinase 3-like-1; Colitis-associated carcinoma; Colorectal cancer; Inflammatory bowel disease; Murine model; Oxidative stress; Ulcerative colitis