Mucin gene expression in biliary epithelial cells

Vandenhaute, Benedicte; Buisine, Marie‐Pierre; Debailleul, Virginie; Clément, Bruno; Moniaux, Nicolas; Dieu, Marie-Claire; Degand, Pierre; Porchet, Nicole; Aubert, Jean‐Pierre

doi:10.1016/s0168-8278(97)80150-x

Cited by 74 publications

(65 citation statements)

References 30 publications

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“…53,54 Overall, the results are quite similar to observations regarding TFF3 in the colon. 26 Understanding the molecular mechanisms of repair reactions in the biliary tree has significant practical implications, particularly for liver allografts.…”

Section: Discussionsupporting

confidence: 86%

Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Nozaki

Lunz

Specht

et al. 2004

The American Journal of Pathology

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Microarray analysis identified trefoil factor family 3 (TFF3) as a gene expressed in biliary epithelial cells (BECs), regulated by interleukin (IL)-6, and potentially involved in biliary pathophysiology. We therefore studied the regulation and function of BEC TFF3, in vitro and in vivo in IL-6 ؉/؉ and IL-6 ؊/؊ mice subjected to chronic bile duct ligation for 12 weeks. In vitro studies showed that IL-6 wild-type (IL-6 ؉/؉ ) BECs expressed higher TFF3 mRNA and protein levels than IL-6-deficient (IL-6 ؊/؊ ) BECs. BEC TFF3 expression is dependent primarily on signal transducer and activator of transcription (STAT3) signaling, but the reciprocal negative regulation known to exist between the intracellular IL-6/gp130 signaling pathways, STAT3 and mitogen-activated protein kinase (MAPK), importantly contributes to BEC TFF3 expression. Specifically blocking STAT3 activity with a dominant-negative molecule or treatment with a growth factor such as hepatocyte growth factor, which increases MAPK signaling, decreases BEC TFF3 expression. In contrast, specifically blocking MAPK activity with PD98059 significantly increased BEC TFF3 expression. Higher BEC TFF3 levels in IL-6 ؉/؉ BECs were associated with significantly better migration than IL-6 ؊/؊ BECs in a wound-healing assay and defective IL-6 ؊/؊ BEC migration was reversed with exogenous TFF3. In vivo, hepatic TFF3 mRNA and protein expression was limited to BECs and dependent significantly on STAT3 signaling, but was influenced by other factors present after bile duct ligation. Com-

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Section: Discussionsupporting

confidence: 86%

Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Nozaki

Lunz

Specht

et al. 2004

The American Journal of Pathology

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“…We have reported that MUC3 is expressed at a low level in hepatocytes in adult liver (Vandenhaute et al 1997). This datum was confirmed in the present study.…”

Section: Accessory Digestive Glandssupporting

confidence: 92%

Developmental Mucin Gene Expression in the Gastroduodenal Tract and Accessory Digestive Glands. II. Duodenum and Liver, Gallbladder, and Pancreas

Buisine

Devisme

Degand

et al. 2000

J Histochem Cytochem.

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107

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S U M M A R YStudies were undertaken to provide information regarding cell-specific expression of mucin genes and their relation to developmental and neoplastic patterns of epithelial cytodifferentiation. In situ hybridization was used to study mRNA expression of mucin genes in duodenum and accessory digestive glands (liver, gallbladder, pancreas) of 13 human embryos and fetuses (6.5-27 weeks' gestation), comparing these with normal and neoplastic adult tissues. These investigations demonstrated that the pattern of mucin gene expression in fetal duodenum reiterated the patterns we observed during gastric and intestinal ontogenesis, with MUC2 and MUC3 expression in the surface epithelium and MUC6 expression associated with the development of Brünner's glands. In embryonic liver, MUC3 was already expressed at 6.5 weeks of gestation in hepatoblasts. As in adults, MUC1, MUC2, MUC3, MUC5AC, MUC5B, and MUC6 were expressed in fetal gallbladder, whereas MUC4 was not. In contrast, MUC4 was strongly expressed in gallbladder adenocarcinomas. MUC5B and MUC6 were expressed in fetal pancreas, from 12 weeks and 26 weeks of gestation, respectively. Surprisingly, MUC3 which is strongly expressed in adult pancreas, was not detected in developmental pancreas. Taken together, these data show complex spatiotemporal regulation of the mucin genes and suggest a possible regulatory role for mucin gene products in gastroduodenal epithelial cell differentiation.

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“…These results suggest that mucin gene expression is tightly regulated. MUC5B is mainly expressed in normal bronchus, submaxillary glands, endocervix, pancreas [4] and gall bladder [5,6]. Interestingly enough, MUC5B has been shown to be highly expressed in colon cancer [3] and especially in the mucus-secreting colon cancer cell lines HT-29 MTX (methotrexate) [7] and LS174T [6].…”

Section: Introductionmentioning

confidence: 99%

Sequence of the 5′-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells

Seuningen¹,

Perrais²,

PIGNY³

et al. 2000

Biochem. J.

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Control of gene expression in intestinal cells is poorly understood. Molecular mechanisms that regulate transcription of cellular genes are the foundation for understanding developmental and differentiation events. Mucin gene expression has been shown to be altered in many intestinal diseases and especially cancers of the gastrointestinal tract. Towards understanding the transcriptional regulation of a member of the 11p15.5 human mucin gene cluster, we have characterized 3.55 kb of the 5h-flanking region of the human mucin gene MUC5B, including the promoter, the first two exons and the first intron. We report here the promoter activity of successively 5h-truncated sections of 956 bases of this region by fusing it to the coding region of a luciferase reporter gene. The transcription start site was determined by primer-extension analysis. The region upstream of the transcription start site is characterized by the presence of a TATA box at bases k32\k26, DNA-binding elements for transcription factors c-Myc, N-Myc, Sp1 and nuclear factor κB as well as putative activator protein (AP)-1-, cAMPresponse-element-binding protein (CREB)-, hepatocyte nuclear

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Mucin gene expression in biliary epithelial cells

Cited by 74 publications

References 30 publications

Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree

Developmental Mucin Gene Expression in the Gastroduodenal Tract and Accessory Digestive Glands. II. Duodenum and Liver, Gallbladder, and Pancreas

Sequence of the 5′-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells

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