June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
BMP-3 is a novel antagonist to TGFβ-2 mediated myofibroblast differentiation in embryonic keratocytes
Author Affiliations & Notes
  • James Wright Spurlin
    Biosciences, Rice University, Houston, TX
  • Peter Y Lwigale
    Biosciences, Rice University, Houston, TX
  • Footnotes
    Commercial Relationships James Spurlin, None; Peter Lwigale, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1301. doi:
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      James Wright Spurlin, Peter Y Lwigale; BMP-3 is a novel antagonist to TGFβ-2 mediated myofibroblast differentiation in embryonic keratocytes. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1301.

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

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Purpose: Embryonic corneas heal scar free and show a transient expression of alpha smooth muscle actin (αSMA). We sought to elucidate the mechanistic regulation of the myofibroblast phenotype transition during scar free corneal regeneration.

Methods: Differential expression of BMPs was screened during various stages of embryonic cornea regeneration via RT-PCR. Spatiotemporal expression of TGFβ-2 and BMP-3 mRNA was identified in sections of regenerating embryonic corneas by in situ hybridization. The temporal response of keratocytes to TGF-β and BMP signaling in regenerating corneas were determined by immunostaining for pSMAD2 and pSMAD1/5/8 respectively. Primary cultures of embryonic keratocytes were treated with BMP-3; a novel antagonist to TGFβ mediated myofibroblast differentiation. To determine the effect of BMP-3 on TGFβ in embryonic keratocytes, the number of αSMA-positive cells was analyzed in primary cultures treated with BMP-3 and/or TGFβ-2. The activity of TGFβ in the presence BMP-3 was assayed by measuring the transcript levels of downstream target genes of TGFβ via qPCR.

Results: Robust expression of TGFβ-2 and BMP-3 was identified in regenerating embryonic corneal stroma and epithelium, respectively. Nuclear localization of pSMAD2 and pSMAD1/5/8 respectively correlated with the expression and down regulation of αSMA. In vitro, BMP-3 was identified as a potent antagonist to the induction of myofibroblast phenotype in primary embryonic keratocytes. Interestingly, transcript analysis indicated that BMP-3 does not inhibit TGFβ mediated expression of αSMA. However, cells treated with BMP-3 expressed low levels of focal adhesion components and assumed a spherical morphology.

Conclusions: These data build a mechanistic model for embryonic cornea regeneration, by which TGFβ mediated myofibroblast differentiation is negatively regulated by BMP-3. While BMP-3 does not directly inhibit TGFβ-2 activity, focal adhesion appears to be abrogated by BMP-3, which may prevent myofibroblast maturation.


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