ArticleMolecular and cellular biology2007
Regulation of mucin gene expression by CREB via a nonclassical retinoic acid signaling pathway.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
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- Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo.Journal of ginseng research · 2022Article
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- The correlation between the vitamin A, D, and E levels and recurrent respiratory tract infections in children of different ages.American journal of translational research · 2021Article
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- Upregulation of FNDC5 gene expression in C2C12 cells after single and combined treatments of resveratrol and ATRA.Lipids in health and disease · 2019Article
- Hedgehog signaling in the airway epithelium of patients with chronic obstructive pulmonary disease.Scientific reports · 2019Article
- Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory Airway Disease.International journal of molecular sciences · 2019Review
- Role of mucins in lung homeostasis: regulated expression and biosynthesis in health and disease.Biochemical Society transactions · 2018Review
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- GSK-3α Is a Novel Target of CREB and CREB-GSK-3α Signaling Participates in Cell Viability in Lung Cancer.PloS one · 2016Article
- Vitamin A Deficiency Impairs Mucin Expression and Suppresses the Mucosal Immune Function of the Respiratory Tract in Chicks.PloS one · 2015Article
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- Induction of chemoresistance by all-trans retinoic acid via a noncanonical signaling in multiple myeloma cells.PloS one · 2014Article
- Virulent Shigella flexneri affects secretion, expression, and glycosylation of gel-forming mucins in mucus-producing cells.Infection and immunity · 2013Article
- The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-induced differentiation of colon cancer cells.BMC cancer · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Vitamin A and its metabolite retinoic acid (RA) are essential elements for normal lung development and the differentiation of lung epithelial cells. We previously showed that RA rapidly activated cyclic AMP response element-binding protein (CREB) in a nonclassical manner in normal human tracheobronchial epithelial (NHTBE) cells. In the present study, we further demonstrated that this nonclassical signaling of RA on the activation of CREB plays a critical role in regulating the expression of airway epithelial cell differentiation markers, the MUC2, MUC5AC, and MUC5B genes. We found that RA rapidly activates the protein kinase Calpha isozyme and transmits the activation signal to CREB via the Raf/MEK/extracellular signal-regulated kinase/p90 ribosomal S6 kinase (RSK) pathway. Activated RSK translocated from the cytoplasm to the nucleus, where it phosphorylates CREB. Activated CREB then binds to a cis-acting replication element motif on the promoter (at nucleotides [nt] -878 to -871) of the MUC5AC gene. The depletion of CREB using small interfering RNA abolished not only the RA-induced MUC5AC but also RA-induced MUC2 and MUC5B. Taken together, our findings demonstrate that CREB activation via this nonclassical RA signaling pathway may play an important role in regulating the expression of mucin genes and mediating the early biological effects of RA during normal mucous differentiation in NHTBE cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.