June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
TGFß INDUCED KFM TRNASFORMATION IN HUMAN CORNEAL FIBROBLASTS IS MODULATED BY YAP AND TAZ
Author Affiliations & Notes
  • SANTOSHI MUPPALA
    Surgical and Radiological Sciences, University of California davis, Davis, California, United States
  • Yeonju Song
    Surgical and Radiological Sciences, University of California davis, Davis, California, United States
  • Eva Rewinski
    Surgical and Radiological Sciences, University of California davis, Davis, California, United States
  • Vijay Krishna Raghunathan
    The Ocular Surface Institute,College of Optometry, Houston, Texas, United States
  • Iman Jalilian
    Surgical and Radiological Sciences, University of California davis, Davis, California, United States
  • Sara M Thomasy
    Surgical and Radiological Sciences, University of California davis, Davis, California, United States
  • Christopher J Murphy
    Surgical and Radiological Sciences, University of California davis, Davis, California, United States
    Ophthalmology and Vision Science, UC Davis School of Medicine, Davis, California, United States
  • Footnotes
    Commercial Relationships   SANTOSHI MUPPALA, None; Yeonju Song, None; Eva Rewinski, None; Vijay Raghunathan, None; Iman Jalilian, None; Sara Thomasy, None; Christopher Murphy, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1419. doi:
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    • Get Citation

      SANTOSHI MUPPALA, Yeonju Song, Eva Rewinski, Vijay Krishna Raghunathan, Iman Jalilian, Sara M Thomasy, Christopher J Murphy; TGFß INDUCED KFM TRNASFORMATION IN HUMAN CORNEAL FIBROBLASTS IS MODULATED BY YAP AND TAZ
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):1419.

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

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Abstract

Purpose : Corneal stromal wound healing is a complex process which integrates a cascade of events including elaboration and remodeling of the extracellular matrix (ECM) and transdifferentiation of quiescent cells in the stroma (keratocytes, to activated fibroblasts and subsequently myofibroblasts-KFM transformation). Transforming Growth Factor ß1 (TGFß1) is elaborated in wounds after injury and promotes KFM transformation. TGFß causes cellular changes through smad transcriptional modulators which result in the phosphorylation of smad2/3 and association with smad4 relocates these proteins to the cell nucleus, accelerating the transcriptional cascade. The novel mechanotransduction factors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ) are strongly implicated in the matrix stiffness. Here, we examined the effects of knockdown of YAP and TAZ on smad2/3/4, TGFß1 induced KFM transformation of human corneal fibroblasts (HCFs).

Methods : We used a knockdown approach to silence YAP and TAZ separately in immortalized human corneal stromal fibroblasts. 24h post siRNA transfection, cells were cultured in the presence or absence of 10ng/ml TGFß1 for 72 hr. The expression of Smad2/3/4 and Alpha Smooth Muscle Actin (αSMA) were assessed by immunostaining and Western blotting. Images were quantitatively analyzed using MATLAB.

Results :
TGFß1 stimulation resulted in the translocation of YAP and TAZ to the nucleus suggesting inhibition of phosphorylation. Specific knockdown of YAP and TAZ decreased TGFß1 induced αSMA (effect of YAP knockdown>TAZ) suggesting YAP and TAZ to play a role in KFM transdifferentiation.

Conclusions : Our findings suggest that YAP and TAZ function as modulators of TGFß1 induced KFM transformation. These results suggest YAP and TAZ represent novel therapeutic targets for improving corneal wound healing outcomes for patients.
I think modulation is more accurate for the state of the investigations to date. Vijay---your thoughts? Also: the data are what the data are but we will need to reconcile the differing results prior to publication. Again, Vijay, your thoughts welcome in devising a work plan towards pblication

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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