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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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Related in: MedlinePlus

Elevated expression of CYP3A4 in MC and normal tissues. (A) Immunofluorescence assay. Red staining indicates protein expression of CYP3A4, while blue staining indicates the nuclei of the cells. Magnification: Left column, ×4; right column, ×20. (B) Immunoblot analysis of the expression of CYP3A4. Results are representative of 19 independent sample tissues per group. Expression of CYP3A4 was standardized to that of GAPDH. MC, melanosis coli.
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f5-mmr-12-04-5807: Elevated expression of CYP3A4 in MC and normal tissues. (A) Immunofluorescence assay. Red staining indicates protein expression of CYP3A4, while blue staining indicates the nuclei of the cells. Magnification: Left column, ×4; right column, ×20. (B) Immunoblot analysis of the expression of CYP3A4. Results are representative of 19 independent sample tissues per group. Expression of CYP3A4 was standardized to that of GAPDH. MC, melanosis coli.

Mentions: P450 families of CYP1, CYP2 and CYP3 are the predominant contributors to the oxidative metabolism of >90% of clinical drugs. CYP3A4 is one of these, and is predominantly present in the intestine. The chip expression data revealed that CYP3A4 was downregulated in MC by 11.0-fold, compared with normal tissue. To further verify the results of the gene chip screening, the expression levels of CYP3A4 were assayed using western blotting and an immunofluorescence assay in the present study. The results indicated that the expression of CYP3A4 in MC was higher than in normal tissue (Fig 5) and were, therefore, in accordance with the results of the gene chip screening.


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)

Elevated expression of CYP3A4 in MC and normal tissues. (A) Immunofluorescence assay. Red staining indicates protein expression of CYP3A4, while blue staining indicates the nuclei of the cells. Magnification: Left column, ×4; right column, ×20. (B) Immunoblot analysis of the expression of CYP3A4. Results are representative of 19 independent sample tissues per group. Expression of CYP3A4 was standardized to that of GAPDH. MC, melanosis coli.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-mmr-12-04-5807: Elevated expression of CYP3A4 in MC and normal tissues. (A) Immunofluorescence assay. Red staining indicates protein expression of CYP3A4, while blue staining indicates the nuclei of the cells. Magnification: Left column, ×4; right column, ×20. (B) Immunoblot analysis of the expression of CYP3A4. Results are representative of 19 independent sample tissues per group. Expression of CYP3A4 was standardized to that of GAPDH. MC, melanosis coli.
Mentions: P450 families of CYP1, CYP2 and CYP3 are the predominant contributors to the oxidative metabolism of >90% of clinical drugs. CYP3A4 is one of these, and is predominantly present in the intestine. The chip expression data revealed that CYP3A4 was downregulated in MC by 11.0-fold, compared with normal tissue. To further verify the results of the gene chip screening, the expression levels of CYP3A4 were assayed using western blotting and an immunofluorescence assay in the present study. The results indicated that the expression of CYP3A4 in MC was higher than in normal tissue (Fig 5) and were, therefore, in accordance with the results of the gene chip screening.

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