ArticleDevelopment (Cambridge, England)2014
TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Skin depletion of Kif3a resembles the pediatric atopic dermatitis transcriptome profile.Human molecular genetics · 2022Pooled it
- Developmental factors drive the compartmentalized and discontinuous maturation of the small intestinal epithelium during the early postnatal period.PLoS biology · 2026Article
- Conjunctival transforming growth factor-β2 and vascular endothelial growth factor in canine keratoconjunctivitis sicca: Baseline alterations, clinical associations, and response to 0.2% cyclosporine therapy.Veterinary world · 2026Article
- Obesity impairs gut repair via AFABP-mediated iron overload in intestinal stem cells.Nature metabolism · 2026Article
- Article
- TSP50 Attenuates DSS-Induced Colitis by Regulating TGF-β Signaling Mediated Maintenance of Intestinal Mucosal Barrier Integrity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Intestinal Barrier Function and Neurodegenerative Disease.CNS & neurological disorders drug targets · 2024Review
- TGF-β Isoforms Affect the Planar and Subepithelial Fibrogenesis of Human Conjunctival Fibroblasts in Different Manners.Biomedicines · 2023Article
- Frizzled 7 modulates goblet and Paneth cell fate, and maintains homeostasis in mouse intestine.Development (Cambridge, England) · 2023Article
- Oxidative Stress in the Anterior Ocular Diseases: Diagnostic and Treatment.Biomedicines · 2023Review
- Roles of growth factors in eye development and ophthalmic diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.Scientific reports · 2021Article
- Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis.Cell reports · 2021Article
- Chemical conversion of human epidermal stem cells into intestinal goblet cells for modeling mucus-microbe interaction and therapy.Science advances · 2021Article
- Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection.Biomaterials · 2021Article
- Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk.Nature communications · 2020Article
- BAP1 is a haploinsufficient tumor suppressor linking chronic pancreatitis to pancreatic cancer in mice.Nature communications · 2020Article
- Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.The ocular surface · 2020Review
- SMAD Signaling Restricts Mucous Cell Differentiation in Human Airway Epithelium.American journal of respiratory cell and molecular biology · 2019Article
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The ocular surface epithelia, including the stratified but non-keratinized corneal, limbal and conjunctival epithelium, in concert with the epidermal keratinized eyelid epithelium, function together to maintain eye health and vision. Abnormalities in cellular proliferation or differentiation in any of these surface epithelia are central in the pathogenesis of many ocular surface disorders. Goblet cells are important secretory cell components of various epithelia, including the conjunctiva; however, mechanisms that regulate goblet cell differentiation in the conjunctiva are not well understood. Herein, we report that conditional deletion of transforming growth factor β receptor II (Tgfbr2) in keratin 14-positive stratified epithelia causes ocular surface epithelial hyperplasia and conjunctival goblet cell expansion that invaginates into the subconjunctival stroma in the mouse eye. We found that, in the absence of an external phenotype, the ocular surface epithelium develops properly, but young mice displayed conjunctival goblet cell expansion, demonstrating that TGFβ signaling is required for normal restriction of goblet cells within the conjunctiva. We observed increased expression of SAM-pointed domain containing ETS transcription factor (SPDEF) in stratified conjunctival epithelial cells in Tgfbr2 cKO mice, suggesting that TGFβ restricted goblet cell differentiation directly by repressing Spdef transcription. Gain of function of Spdef in keratin 14-positive epithelia resulted in the ectopic formation of goblet cells in the eyelid and peripheral cornea in adult mice. We found that Smad3 bound two distinct sites on the Spdef promoter and that treatment of keratin 14-positive cells with TGFβ inhibited SPDEF activation, thereby identifying a novel mechanistic role for TGFβ in regulating goblet cell differentiation.
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Registered trials
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.