FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro

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)-β1 and -β3 as modulators in corneal wound healing and fibrosis...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Vincent Yeung, Sriniwas Sriram, Jennifer A. Tran, Xiaoqing Guo, Audrey E. K. Hutcheon, James D. Zieske, Dimitrios Karamichos, Joseph B. Ciolino
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	3D cell culture corneal scarring extracellular matrix (ECM) focal adhesion kinase (FAK) α-smooth muscle actin (αSMA) Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/392e63b66603462983e9326a3b179321
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:392e63b66603462983e9326a3b179321
record_format	dspace
spelling	oai:doaj.org-article:392e63b66603462983e9326a3b1793212021-11-25T16:53:47ZFAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro10.3390/biom111116822218-273Xhttps://doaj.org/article/392e63b66603462983e9326a3b1793212021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1682https://doaj.org/toc/2218-273XCorneal 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)-β1 and -β3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of α-smooth muscle actin (αSMA), 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-β1, TGF-β3, or TGF-β1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-β1 or TGF-β3 impart distinct effects on genes involved in wound healing and fibrosis—<i>ITGAV</i>, <i>ITGB1</i>, <i>SRC</i> and <i>ACTA2</i>. Notably, in the 3D construct model, TGF-β1 enhanced αSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-β3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-β1 + FAKi attenuated TGF-β1-mediated myofibroblast differentiation, as shown by abrogated αSMA expression. This study concludes that FAK signaling is important for the onset of TGF-β1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.Vincent YeungSriniwas SriramJennifer A. TranXiaoqing GuoAudrey E. K. HutcheonJames D. ZieskeDimitrios KaramichosJoseph B. CiolinoMDPI AGarticle3D cell culturecorneal scarringextracellular matrix (ECM)focal adhesion kinase (FAK)α-smooth muscle actin (αSMA)MicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1682, p 1682 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D cell culture corneal scarring extracellular matrix (ECM) focal adhesion kinase (FAK) α-smooth muscle actin (αSMA) Microbiology QR1-502
spellingShingle	3D cell culture corneal scarring extracellular matrix (ECM) focal adhesion kinase (FAK) α-smooth muscle actin (αSMA) Microbiology QR1-502 Vincent Yeung Sriniwas Sriram Jennifer A. Tran Xiaoqing Guo Audrey E. K. Hutcheon James D. Zieske Dimitrios Karamichos Joseph B. Ciolino FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
description	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)-β1 and -β3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of α-smooth muscle actin (αSMA), 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-β1, TGF-β3, or TGF-β1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-β1 or TGF-β3 impart distinct effects on genes involved in wound healing and fibrosis—<i>ITGAV</i>, <i>ITGB1</i>, <i>SRC</i> and <i>ACTA2</i>. Notably, in the 3D construct model, TGF-β1 enhanced αSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-β3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-β1 + FAKi attenuated TGF-β1-mediated myofibroblast differentiation, as shown by abrogated αSMA expression. This study concludes that FAK signaling is important for the onset of TGF-β1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.
format	article
author	Vincent Yeung Sriniwas Sriram Jennifer A. Tran Xiaoqing Guo Audrey E. K. Hutcheon James D. Zieske Dimitrios Karamichos Joseph B. Ciolino
author_facet	Vincent Yeung Sriniwas Sriram Jennifer A. Tran Xiaoqing Guo Audrey E. K. Hutcheon James D. Zieske Dimitrios Karamichos Joseph B. Ciolino
author_sort	Vincent Yeung
title	FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
title_short	FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
title_full	FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
title_fullStr	FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
title_full_unstemmed	FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
title_sort	fak inhibition attenuates corneal fibroblast differentiation in vitro
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/392e63b66603462983e9326a3b179321
work_keys_str_mv	AT vincentyeung fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT sriniwassriram fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT jenniferatran fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT xiaoqingguo fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT audreyekhutcheon fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT jamesdzieske fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT dimitrioskaramichos fakinhibitionattenuatescornealfibroblastdifferentiationinvitro AT josephbciolino fakinhibitionattenuatescornealfibroblastdifferentiationinvitro
_version_	1718412887069818880

FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro

Ejemplares similares