ArticleInvestigative ophthalmology & visual science2011
Notch signaling modulates MUC16 biosynthesis in an in vitro model of human corneal and conjunctival epithelial cell differentiation.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- The O-GlcNAc modification promotes terminal differentiation of human corneal epithelial cells.Glycobiology · 2020Article
- Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway.Development (Cambridge, England) · 2016Article
- Establishment of a novel in vitro model of stratified epithelial wound healing with barrier function.Scientific reports · 2016Article
- Wakayama symposium: role of canonical Notch signaling in conjucntival goblet cell differentiation and dry eye syndrome.BMC ophthalmology · 2015Article
- Understanding the Unique Attributes of MUC16 (CA125): Potential Implications in Targeted Therapy.Cancer research · 2015Review
- Membrane proximal ectodomain cleavage of MUC16 occurs in the acidifying Golgi/post-Golgi compartments.Scientific reports · 2015Article
- Expression analysis of the transmembrane mucin MUC20 in human corneal and conjunctival epithelia.Investigative ophthalmology & visual science · 2014Article
- Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium.Molecular vision · 2014Article
- Tear film mucins: front line defenders of the ocular surface; comparison with airway and gastrointestinal tract mucins.Experimental eye research · 2013Article
- The ocular surface epithelial barrier and other mechanisms of mucosal protection: from allergy to infectious diseases.Current opinion in allergy and clinical immunology · 2013Review
- A novel fluorescent lipid probe for dry eye: retrieval by tear lipocalin in humans.Investigative ophthalmology & visual science · 2013Article
- Mastermind-like transcriptional co-activator-mediated Notch signaling is indispensable for maintaining conjunctival epithelial identity.Development (Cambridge, England) · 2013Article
- Article
- Differential contribution of hypertonic electrolytes to corneal epithelial dysfunction.Experimental eye research · 2012Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
purposeNotch proteins are a family of transmembrane receptors that coordinate binary cell fate decisions and differentiation in wet-surfaced epithelia. We sought to determine whether Notch signaling contributes to maintaining mucosal homeostasis by modulating the biosynthesis of cell surface-associated mucins in an in vitro model of human corneal (HCLE) and conjunctival (HCjE) epithelial cell differentiation.
methodsHCLE and HCjE cells were grown at different stages of differentiation, representing nondifferentiated (preconfluent and confluent) and differentiated (stratified) epithelial cultures. Notch signaling was blocked with the γ-secretase inhibitor dibenzazepine (DBZ). The presence of Notch intracellular domains (Notch1 to Notch3) and mucin protein (MUC1, -4, -16) was evaluated by electrophoresis and Western blot analysis. Mucin gene expression was determined by TaqMan real-time polymerase chain reaction.
resultsHere we demonstrate that Notch3 is highly expressed in undifferentiated and differentiated HCLE and HCjE cells, and that Notch1 and Notch2 biosynthesis is enhanced by induction of differentiation with serum-containing media. Inhibition of Notch signaling with DBZ impaired MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells at both preconfluent and confluent stages, but not in postmitotic stratified cells. In contrast to protein levels, the amount of MUC16 transcripts were not significantly reduced after DBZ treatment, suggesting that Notch regulates MUC16 posttranscriptionally. Immunoblots of DBZ-treated epithelial cells grown at different stages of differentiation revealed no differences in the levels of MUC1 and MUC4.
conclusionsThese results indicate that MUC16 biosynthesis is posttranscriptionally regulated by Notch signaling at early stages of epithelial cell differentiation, and suggest that Notch activation contributes to maintaining a mucosal phenotype at the ocular surface.
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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.