FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro




Yeung, Vincent
Sriram, Sriniwas
Tran, Jennifer A.
Guo, Xiaoqing
Hutcheon, Audrey E. K.
Zieske, James D.
Karamichos, Dimitrios
Ciolino, Joseph B.


0000-0002-8761-3824 (Karamichos, Dimitrios)

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Corneal fibrosis (or scarring) occurs in response to ocular trauma or infection, and by reducing corneal transparency, it can lead to visual impairment and blindness. Studies highlight important roles for transforming growth factor (TGF)-beta1 and -beta3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of alpha-smooth muscle actin (alphaSMA), a myofibroblast marker. In this study, human corneal fibroblasts (hCF) were cultured as a monolayer culture (2D) or on poly-transwell membranes to generate corneal stromal constructs (3D) that were treated with TGF-beta1, TGF-beta3, or TGF-beta1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-beta1 or TGF-beta3 impart distinct effects on genes involved in wound healing and fibrosis-ITGAV, ITGB1, SRC and ACTA2. Notably, in the 3D construct model, TGF-beta1 enhanced alphaSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-beta3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-beta1 + FAKi attenuated TGF-beta1-mediated myofibroblast differentiation, as shown by abrogated alphaSMA expression. This study concludes that FAK signaling is important for the onset of TGF-beta1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.



Yeung, V., Sriram, S., Tran, J. A., Guo, X., Hutcheon, A., Zieske, J. D., Karamichos, D., & Ciolino, J. B. (2021). FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro. Biomolecules, 11(11), 1682. https://doi.org/10.3390/biom11111682


© 2021 by the authors.


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