Mucosal pentraxin (Mptx), a novel rat gene 10-fold down-regulated in colon by dietary heme.
Consumption of red meat is associated with increased colon cancer risk. Our previous work indicated that this association might be due to the heme content of red meat. In rat studies, dietary heme increased colonic cytotoxicity and epithelial cell turnover, carcinogenesis biomarkers. Here we apply DNA microarray technology to examine effects of heme on colonic gene expression. A rat colon-specific microarray was constructed and hybridized in duplicate to RNA extracts from colon scrapings of rats fed diets with or without heme (n=6-7). We were able to reproducibly identify changes in colonic mRNA abundance in response to heme. Most striking was a >10-fold down-regulation of a single rat gene, an unprecedented gene-modulating effect of a dietary component. Based on homology, the novel gene encodes a pentraxin, the first identified in colon. Pentraxins are postulated to be involved in dealing with dying cells. Quantitative PCR confirmed the strong heme-induced down-regulation of this gene, which we named mucosal pentraxin (Mptx). Overall, our data support the efficacy of cDNA array expression profiling to investigate effects of specific nutrients in an in vivo system and may provide an approach to establishing markers for diet-induced stress of mammalian colonic mucosa.
Van Der Meer-Van Kraaij
Cindy
C
Wageningen Centre for Food Sciences (WCFS), RIKILT, Institute of Food Safety, 6700 AE, Wageningen, The Netherlands.
Van Lieshout
Esther M M
EM
Kramer
Evelien
E
Van Der Meer
Roelof
R
Keijer
Jaap
J
D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism; D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003106:Colon / Q000378:metabolism*; D004032:Diet; D015536:Down-Regulation; D040461:Gene Components; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006418:Heme / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017385:Sequence Homology
D000209:Acute-Phase Proteins; C475505:Mptx1 protein, rat; D012333:RNA, Messenger; D006418:Heme