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Triiodothyronine represses MUC5AC expression by antagonizing Sp1 binding to its promoter in human bronchial epithelial HBE16 cells.

Wang X, Li Q, Zhou X, Kolosov VP, Perelman JM - J. Biomed. Biotechnol. (2012)

Bottom Line: Interestingly, in this condition thyroid function is impaired with decreased level of triiodothyronine (T3), indicating potential link between low level of T3 and mucus hypersecretion.In this study we aimed to elucidate the effect of T3 on MUC5AC secretion in human bronchial epithelial HBE16 cells and further investigate how T3 regulates MUC5AC gene expression at transcriptional level.Our results suggest that decreased T3 level leads to the release of repression of MUC5AC expression and thus contributes to mucus hypersecretion.

View Article: PubMed Central - PubMed

Affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

ABSTRACT
Mucus hypersecretion is a distinguished feature of chronic inflammatory airway diseases. Interestingly, in this condition thyroid function is impaired with decreased level of triiodothyronine (T3), indicating potential link between low level of T3 and mucus hypersecretion. But the underlying mechanisms are poorly understood. In this study we aimed to elucidate the effect of T3 on MUC5AC secretion in human bronchial epithelial HBE16 cells and further investigate how T3 regulates MUC5AC gene expression at transcriptional level. By RT-PCR and ELISA we showed that T3 inhibited MUC5AC mRNA expression and protein secretion in HBE16 cells. Furthermore, luciferase assay and site-directed mutagenesis analysis demonstrated that T3 repressed MUC5AC expression at transcriptional level and the mechanism might partly lie in the specific inhibition of Sp1 binding to the promoter. Our results suggest that decreased T3 level leads to the release of repression of MUC5AC expression and thus contributes to mucus hypersecretion.

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T3 inhibits the transcription of MUC5AC in HBE16 cells. The luciferase activity was determined as described in Materials and Methods. Control group: different MUC5AC promoter plasmids in the absence of T3; experimental group: different MUC5AC promoter plasmids in the presence of T3.*P < 0.01 versus pGL3-basic control group; **P > 0.05 versus pGL3-basic control group; #P > 0.05 versus the same promoter control group; ##P < 0.01 versus the same promoter control group.
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fig2: T3 inhibits the transcription of MUC5AC in HBE16 cells. The luciferase activity was determined as described in Materials and Methods. Control group: different MUC5AC promoter plasmids in the absence of T3; experimental group: different MUC5AC promoter plasmids in the presence of T3.*P < 0.01 versus pGL3-basic control group; **P > 0.05 versus pGL3-basic control group; #P > 0.05 versus the same promoter control group; ##P < 0.01 versus the same promoter control group.

Mentions: To explore whether T3 regulates MUC5AC expression at transcriptional level, different regions of MUC5AC promoter were characterized. As shown in Figure 2, the luciferase activity was significantly upregulated in HEB16 cells transfected with MUC5AC promoter constructs containing fragment −1,330/+48, −689/+48, −324/+48 (P < 0.01) but not −64/+48 (P > 0.05) as compared with pGL3-basic vector control group, suggesting that −324/+48 comprises the effective region for transcriptional regulation of MUC5AC. Notably T3 showed inhibitory effect on luciferase activity only with MUC5AC promoter construct containing fragment −324/+48, thus indicating that T3 indeed regulates MUC5AC expression at transcriptional level.


Triiodothyronine represses MUC5AC expression by antagonizing Sp1 binding to its promoter in human bronchial epithelial HBE16 cells.

Wang X, Li Q, Zhou X, Kolosov VP, Perelman JM - J. Biomed. Biotechnol. (2012)

T3 inhibits the transcription of MUC5AC in HBE16 cells. The luciferase activity was determined as described in Materials and Methods. Control group: different MUC5AC promoter plasmids in the absence of T3; experimental group: different MUC5AC promoter plasmids in the presence of T3.*P < 0.01 versus pGL3-basic control group; **P > 0.05 versus pGL3-basic control group; #P > 0.05 versus the same promoter control group; ##P < 0.01 versus the same promoter control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303580&req=5

fig2: T3 inhibits the transcription of MUC5AC in HBE16 cells. The luciferase activity was determined as described in Materials and Methods. Control group: different MUC5AC promoter plasmids in the absence of T3; experimental group: different MUC5AC promoter plasmids in the presence of T3.*P < 0.01 versus pGL3-basic control group; **P > 0.05 versus pGL3-basic control group; #P > 0.05 versus the same promoter control group; ##P < 0.01 versus the same promoter control group.
Mentions: To explore whether T3 regulates MUC5AC expression at transcriptional level, different regions of MUC5AC promoter were characterized. As shown in Figure 2, the luciferase activity was significantly upregulated in HEB16 cells transfected with MUC5AC promoter constructs containing fragment −1,330/+48, −689/+48, −324/+48 (P < 0.01) but not −64/+48 (P > 0.05) as compared with pGL3-basic vector control group, suggesting that −324/+48 comprises the effective region for transcriptional regulation of MUC5AC. Notably T3 showed inhibitory effect on luciferase activity only with MUC5AC promoter construct containing fragment −324/+48, thus indicating that T3 indeed regulates MUC5AC expression at transcriptional level.

Bottom Line: Interestingly, in this condition thyroid function is impaired with decreased level of triiodothyronine (T3), indicating potential link between low level of T3 and mucus hypersecretion.In this study we aimed to elucidate the effect of T3 on MUC5AC secretion in human bronchial epithelial HBE16 cells and further investigate how T3 regulates MUC5AC gene expression at transcriptional level.Our results suggest that decreased T3 level leads to the release of repression of MUC5AC expression and thus contributes to mucus hypersecretion.

View Article: PubMed Central - PubMed

Affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

ABSTRACT
Mucus hypersecretion is a distinguished feature of chronic inflammatory airway diseases. Interestingly, in this condition thyroid function is impaired with decreased level of triiodothyronine (T3), indicating potential link between low level of T3 and mucus hypersecretion. But the underlying mechanisms are poorly understood. In this study we aimed to elucidate the effect of T3 on MUC5AC secretion in human bronchial epithelial HBE16 cells and further investigate how T3 regulates MUC5AC gene expression at transcriptional level. By RT-PCR and ELISA we showed that T3 inhibited MUC5AC mRNA expression and protein secretion in HBE16 cells. Furthermore, luciferase assay and site-directed mutagenesis analysis demonstrated that T3 repressed MUC5AC expression at transcriptional level and the mechanism might partly lie in the specific inhibition of Sp1 binding to the promoter. Our results suggest that decreased T3 level leads to the release of repression of MUC5AC expression and thus contributes to mucus hypersecretion.

Show MeSH
Related in: MedlinePlus