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Histopathology of melanosis coli and determination of its associated genes by comparative analysis of expression microarrays.

Li XΑ, Zhou Y, Zhou SΧ, Liu HR, Xu JM, Gao L, Yu XJ, Li XH - Mol Med Rep (2015)

Bottom Line: The results demonstrated that the pigment deposits in MC consisted of lipofuscin.Western blotting and immunofluorescence assays indicated that the expression of CYP3A4 in the normal tissue was higher than in the MC tissue.The results of the present study provided a comprehensive description of the histopathological characteristics and pathogenesis of MC and for the first time, to the best of our knowledge, demonstrated that the cytochrome P450‑associated genes were significantly downregulated in melanosis coli.

View Article: PubMed Central - PubMed

Affiliation: The Gastroenterology Tumor and Microenvironment Laboratory, Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, Sichuan 610041, P.R. China.

ABSTRACT
Melanosis coli (MC) refers to the condition characterized by abnormal brown or black pigmentation deposits on the colonic mucosa. However, the histopathological findings and genes associated with the pathogenesis of melanosis coli remain to be fully elucidated. The present study aimed to examine the histopathological features and differentially expressed genes of MC. This involved performing hematoxylin and eosin staining, specific staining and immunohistochemistry on tissues sections, which were isolated from patients diagnosed with MC. DNA expression microarray analysis, western blotting and immunofluorescence assays were performed to analyze the differentially expressed genes of melanosis coli. The results demonstrated that the pigment deposits in MC consisted of lipofuscin. A TUNEL assay revealed that a substantial number of apoptotic cells were present within the macrophages and superficial lamina propria of the colonic epithelium. Expression microarray analysis revealed that the significantly downregulated genes were CYP3A4, CYP3A7, UGT2B11 and UGT2B15 in melanosis coli. Western blotting and immunofluorescence assays indicated that the expression of CYP3A4 in the normal tissue was higher than in the MC tissue. The results of the present study provided a comprehensive description of the histopathological characteristics and pathogenesis of MC and for the first time, to the best of our knowledge, demonstrated that the cytochrome P450‑associated genes were significantly downregulated in melanosis coli. This novel information can be used to assist in further investigations of melanosis coli.

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Differentially expressed genes in MC, determined using expression microarray analysis. (A) Total RNA of the samples: Lane 1–2, donors where endoscopic examination revealed MC; lane 3–4, donors where endoscopic examination demonstrated no abnormalities. (B) Heat map for signature genes in each group. Color scale, log2-transformed expression (red, high; green, low) for each gene (row) normalized by the mean of all samples. (C) Volcano plot representation of the differentially expressed genes. The vertical green lines on the left and right correspond to 2.0-fold downregulation and upregulation, respectively, and the horizontal line indicates a P-value of 0.05. The red points in the plot indicate the differentially expressed genes between the normal and MC with statistical significance. MC, melanosis coli.
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f4-mmr-12-04-5807: Differentially expressed genes in MC, determined using expression microarray analysis. (A) Total RNA of the samples: Lane 1–2, donors where endoscopic examination revealed MC; lane 3–4, donors where endoscopic examination demonstrated no abnormalities. (B) Heat map for signature genes in each group. Color scale, log2-transformed expression (red, high; green, low) for each gene (row) normalized by the mean of all samples. (C) Volcano plot representation of the differentially expressed genes. The vertical green lines on the left and right correspond to 2.0-fold downregulation and upregulation, respectively, and the horizontal line indicates a P-value of 0.05. The red points in the plot indicate the differentially expressed genes between the normal and MC with statistical significance. MC, melanosis coli.

Mentions: Data from three independent samples demonstrated that 1,718 genes were differentially expressed between the MC and control samples (Fig. 4). Of these, 879 genes were downregulated and 739 genes were upregulated, as shown by the Volcano plot representation in Fig. 4C. The most significantly upregulated genes were CCL18, NEFM, EGF and IL15RA, and the most significantly downregulated genes were CYP3A4, CYP3A7, UGT2B11 and UGT2B15 (Fig. 4B). The GO functional class scoring of the differentially expressed genes demonstrated that the most affected categories were as follows: Immune response, lymphocyte activation, humoral immune response, cell chemotaxis, G-protein-coupled chemoattractant receptor activity, CCR chemokine receptor binding and drug catabolic process for the downregulated genes and chemokine receptor binding, enzyme inhibitor activity, acid/thiol ligase activity, bile acid transmembrane transporter activity, cellular response to inorganic substance and lipoprotein particle for the upregulated genes (Table II). Accordingly, the most affected pathways for the downregulated genes were as follows: Immune network, NF-κB signaling pathway, metabolism of xenobiotics by cytochrome P450, vitamin digestion and absorption (Table III) the most affected pathways for the upregulated genes were as follows: Salmonella infection, mineral absorption, bile secretion, collecting duct acid secretion and melanoma (Table IV).


Histopathology of melanosis coli and determination of its associated genes by comparative analysis of expression microarrays.

Li XΑ, Zhou Y, Zhou SΧ, Liu HR, Xu JM, Gao L, Yu XJ, Li XH - Mol Med Rep (2015)

Differentially expressed genes in MC, determined using expression microarray analysis. (A) Total RNA of the samples: Lane 1–2, donors where endoscopic examination revealed MC; lane 3–4, donors where endoscopic examination demonstrated no abnormalities. (B) Heat map for signature genes in each group. Color scale, log2-transformed expression (red, high; green, low) for each gene (row) normalized by the mean of all samples. (C) Volcano plot representation of the differentially expressed genes. The vertical green lines on the left and right correspond to 2.0-fold downregulation and upregulation, respectively, and the horizontal line indicates a P-value of 0.05. The red points in the plot indicate the differentially expressed genes between the normal and MC with statistical significance. MC, melanosis coli.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581826&req=5

f4-mmr-12-04-5807: Differentially expressed genes in MC, determined using expression microarray analysis. (A) Total RNA of the samples: Lane 1–2, donors where endoscopic examination revealed MC; lane 3–4, donors where endoscopic examination demonstrated no abnormalities. (B) Heat map for signature genes in each group. Color scale, log2-transformed expression (red, high; green, low) for each gene (row) normalized by the mean of all samples. (C) Volcano plot representation of the differentially expressed genes. The vertical green lines on the left and right correspond to 2.0-fold downregulation and upregulation, respectively, and the horizontal line indicates a P-value of 0.05. The red points in the plot indicate the differentially expressed genes between the normal and MC with statistical significance. MC, melanosis coli.
Mentions: Data from three independent samples demonstrated that 1,718 genes were differentially expressed between the MC and control samples (Fig. 4). Of these, 879 genes were downregulated and 739 genes were upregulated, as shown by the Volcano plot representation in Fig. 4C. The most significantly upregulated genes were CCL18, NEFM, EGF and IL15RA, and the most significantly downregulated genes were CYP3A4, CYP3A7, UGT2B11 and UGT2B15 (Fig. 4B). The GO functional class scoring of the differentially expressed genes demonstrated that the most affected categories were as follows: Immune response, lymphocyte activation, humoral immune response, cell chemotaxis, G-protein-coupled chemoattractant receptor activity, CCR chemokine receptor binding and drug catabolic process for the downregulated genes and chemokine receptor binding, enzyme inhibitor activity, acid/thiol ligase activity, bile acid transmembrane transporter activity, cellular response to inorganic substance and lipoprotein particle for the upregulated genes (Table II). Accordingly, the most affected pathways for the downregulated genes were as follows: Immune network, NF-κB signaling pathway, metabolism of xenobiotics by cytochrome P450, vitamin digestion and absorption (Table III) the most affected pathways for the upregulated genes were as follows: Salmonella infection, mineral absorption, bile secretion, collecting duct acid secretion and melanoma (Table IV).

Bottom Line: The results demonstrated that the pigment deposits in MC consisted of lipofuscin.Western blotting and immunofluorescence assays indicated that the expression of CYP3A4 in the normal tissue was higher than in the MC tissue.The results of the present study provided a comprehensive description of the histopathological characteristics and pathogenesis of MC and for the first time, to the best of our knowledge, demonstrated that the cytochrome P450‑associated genes were significantly downregulated in melanosis coli.

View Article: PubMed Central - PubMed

Affiliation: The Gastroenterology Tumor and Microenvironment Laboratory, Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, Sichuan 610041, P.R. China.

ABSTRACT
Melanosis coli (MC) refers to the condition characterized by abnormal brown or black pigmentation deposits on the colonic mucosa. However, the histopathological findings and genes associated with the pathogenesis of melanosis coli remain to be fully elucidated. The present study aimed to examine the histopathological features and differentially expressed genes of MC. This involved performing hematoxylin and eosin staining, specific staining and immunohistochemistry on tissues sections, which were isolated from patients diagnosed with MC. DNA expression microarray analysis, western blotting and immunofluorescence assays were performed to analyze the differentially expressed genes of melanosis coli. The results demonstrated that the pigment deposits in MC consisted of lipofuscin. A TUNEL assay revealed that a substantial number of apoptotic cells were present within the macrophages and superficial lamina propria of the colonic epithelium. Expression microarray analysis revealed that the significantly downregulated genes were CYP3A4, CYP3A7, UGT2B11 and UGT2B15 in melanosis coli. Western blotting and immunofluorescence assays indicated that the expression of CYP3A4 in the normal tissue was higher than in the MC tissue. The results of the present study provided a comprehensive description of the histopathological characteristics and pathogenesis of MC and for the first time, to the best of our knowledge, demonstrated that the cytochrome P450‑associated genes were significantly downregulated in melanosis coli. This novel information can be used to assist in further investigations of melanosis coli.

Show MeSH
Related in: MedlinePlus