Transforming growth factor β inhibits MUC5AC expression by Smad3/HDAC2 complex formation and NF-κB deacetylation at K310 in NCI-H292 cells

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dc.contributor.authorSu Ui Lee-
dc.contributor.authorMun-Ock Kim-
dc.contributor.authorMyung Ji Kang-
dc.contributor.authorEun Sol Oh-
dc.contributor.authorH Ro-
dc.contributor.authorRo-Woon Lee-
dc.contributor.authorYu Na Song-
dc.contributor.authorSunin Jung-
dc.contributor.authorJae-Won Lee-
dc.contributor.authorSoo Yun Lee-
dc.contributor.authorTaeyeol Bae-
dc.contributor.authorS T Hong-
dc.contributor.authorTae-Don Kim-
dc.date.accessioned2021-02-03T03:30:30Z-
dc.date.available2021-02-03T03:30:30Z-
dc.date.issued2021-
dc.identifier.issn1016-8478-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/24054-
dc.description.abstractAirway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel- forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.-
dc.publisherKorea Soc-Assoc-Inst-
dc.titleTransforming growth factor β inhibits MUC5AC expression by Smad3/HDAC2 complex formation and NF-κB deacetylation at K310 in NCI-H292 cells-
dc.title.alternativeTransforming growth factor β inhibits MUC5AC expression by Smad3/HDAC2 complex formation and NF-κB deacetylation at K310 in NCI-H292 cells-
dc.typeArticle-
dc.citation.titleMolecules and Cells-
dc.citation.number1-
dc.citation.endPage49-
dc.citation.startPage38-
dc.citation.volume44-
dc.contributor.affiliatedAuthorSu Ui Lee-
dc.contributor.affiliatedAuthorMun-Ock Kim-
dc.contributor.affiliatedAuthorMyung Ji Kang-
dc.contributor.affiliatedAuthorEun Sol Oh-
dc.contributor.affiliatedAuthorRo-Woon Lee-
dc.contributor.affiliatedAuthorYu Na Song-
dc.contributor.affiliatedAuthorSunin Jung-
dc.contributor.affiliatedAuthorJae-Won Lee-
dc.contributor.affiliatedAuthorSoo Yun Lee-
dc.contributor.affiliatedAuthorTaeyeol Bae-
dc.contributor.affiliatedAuthorTae-Don Kim-
dc.contributor.alternativeName이수의-
dc.contributor.alternativeName김문옥-
dc.contributor.alternativeName강명지-
dc.contributor.alternativeName오은솔-
dc.contributor.alternativeName노현주-
dc.contributor.alternativeName이로운-
dc.contributor.alternativeName송유나-
dc.contributor.alternativeName정선인-
dc.contributor.alternativeName이재원-
dc.contributor.alternativeName이수연-
dc.contributor.alternativeName배태열-
dc.contributor.alternativeName홍성태-
dc.contributor.alternativeName김태돈-
dc.identifier.bibliographicCitationMolecules and Cells, vol. 44, no. 1, pp. 38-49-
dc.identifier.doi10.14348/molcells.2020.0188-
dc.subject.keywordHDAC2-
dc.subject.keywordMUC5AC-
dc.subject.keywordNF-κB-
dc.subject.keywordSmad3-
dc.subject.keywordTransforming growth factor β-
dc.subject.localHDAC2-
dc.subject.localMUC5AC-
dc.subject.localNFkappaB-
dc.subject.localNFκB-
dc.subject.localNf-κB-
dc.subject.localNf-κb-
dc.subject.localNuclear factor (NF)-κB-
dc.subject.localNuclear factor kappa B-
dc.subject.localNuclear factor kappaB-
dc.subject.localNuclear factor κB-
dc.subject.localNuclear factor κB (NF-κB)-
dc.subject.localNuclear factor-kappa B-
dc.subject.localNuclear factor-kappa B (NF-κB)-
dc.subject.localNuclear factor-kappaB-
dc.subject.localNuclear factor-κB-
dc.subject.localNuclear factor-κb-
dc.subject.localNF-kB-
dc.subject.localNF-kappa B-
dc.subject.localNF-kappaB-
dc.subject.localNF-ΚB-
dc.subject.localNF-κ B-
dc.subject.localNF-κB-
dc.subject.localNF-κB (nuclear factor kappa-B)-
dc.subject.localnuclear factor kappa B-
dc.subject.localnuclear factor κB-
dc.subject.localnuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB (NF-κB)-
dc.subject.localnuclear factor-κB-
dc.subject.localnuclear factorκB-
dc.subject.localSmad3-
dc.subject.localTransforming growth factor beta-
dc.subject.localTransforming growth factor-β-
dc.subject.localTransforming growth factor β-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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