June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium
Author Affiliations & Notes
  • Chia-Yang Liu
    Ophthalmology, Univ of Cincinnati, Cincinnati, OH
  • Yujin Zhang
    Ophthalmology, Univ of Cincinnati, Cincinnati, OH
  • Footnotes
    Commercial Relationships Chia-Yang Liu, None; Yujin Zhang, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3021. doi:
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      Chia-Yang Liu, Yujin Zhang; TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3021.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: To demonstrate the signaling transduction of TGFbRII→Smads⊣SPDEF→Muc5/ac axis for conjunctival goblet cell differentiation.

Methods: We employed conditional deletion of transforming growth factor β receptor II (TGFβRII) in keratin 14-positive stratified epithelia. Phenotypic and biochemical analyses of the resultant ocular surface were compared to the wild-type littermates at various stages.

Results: 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 TGFβRII cKO mice, suggesting that TGFβ restricted goblet cell differentiation directly by repressing Spdef transcription. Gain-of-function of Spdef in keratin 14-derived 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 derived cells with TGFβ inhibited SPDEF activation, thereby identifying a novel mechanistic role for TGFβ in regulating goblet cell differentiation.

Conclusions: TGFbRII-Smads is the upstream regulator of Spdef during conjunctival goblet cell differentiation.


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