Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro

Abstract Transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signaling pathways play important roles in the proliferation and differentiation of lens epithelial cells (LECs) during development. Low dosage bFGF promotes cell proliferation while high dosage induces differentiation....

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Autores principales: Dong Wang, Eddie Wang, Kelsey Liu, Chun-hong Xia, Song Li, Xiaohua Gong
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/2f183bf36d2643e7a4bf43af4296f009
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spelling oai:doaj.org-article:2f183bf36d2643e7a4bf43af4296f0092021-12-02T15:06:01ZRoles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro10.1038/s41598-017-07619-52045-2322https://doaj.org/article/2f183bf36d2643e7a4bf43af4296f0092017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07619-5https://doaj.org/toc/2045-2322Abstract Transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signaling pathways play important roles in the proliferation and differentiation of lens epithelial cells (LECs) during development. Low dosage bFGF promotes cell proliferation while high dosage induces differentiation. TGFβ signaling regulates LEC proliferation and differentiation as well, but also promotes epithelial-mesenchymal transitions that lead to cataracts. Thus far, it has been difficult to recapitulate the features of germinative LECs in vitro. Here, we have established a LEC culture protocol that uses SB431542 (SB) compound to inhibit TGFβ/Smad activation, and found that SB treatment promoted mouse LEC proliferation, maintained LECs’ morphology and distinct markers including N-cadherin, c-Maf, Prox1, and αA-, αB-, and β-crystallins. In contrast, low-dosage bFGF was unable to sustain those markers and, combined with SB, altered LECs’ morphology and β-crystallin expression. We further found that Matrigel substrate coatings greatly increased cell proliferation and uniquely affected β-crystallin expression. Cultured LECs retained the ability to differentiate into γ-crystallin-positive lentoids by high-dosage bFGF treatment. Thus, a suppression of TGFβ/Smad signaling in vitro is critical to maintaining characteristic features of mouse LECs, especially expression of the key transcription factors c-Maf and Prox1.Dong WangEddie WangKelsey LiuChun-hong XiaSong LiXiaohua GongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Dong Wang
Eddie Wang
Kelsey Liu
Chun-hong Xia
Song Li
Xiaohua Gong
Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro
description Abstract Transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signaling pathways play important roles in the proliferation and differentiation of lens epithelial cells (LECs) during development. Low dosage bFGF promotes cell proliferation while high dosage induces differentiation. TGFβ signaling regulates LEC proliferation and differentiation as well, but also promotes epithelial-mesenchymal transitions that lead to cataracts. Thus far, it has been difficult to recapitulate the features of germinative LECs in vitro. Here, we have established a LEC culture protocol that uses SB431542 (SB) compound to inhibit TGFβ/Smad activation, and found that SB treatment promoted mouse LEC proliferation, maintained LECs’ morphology and distinct markers including N-cadherin, c-Maf, Prox1, and αA-, αB-, and β-crystallins. In contrast, low-dosage bFGF was unable to sustain those markers and, combined with SB, altered LECs’ morphology and β-crystallin expression. We further found that Matrigel substrate coatings greatly increased cell proliferation and uniquely affected β-crystallin expression. Cultured LECs retained the ability to differentiate into γ-crystallin-positive lentoids by high-dosage bFGF treatment. Thus, a suppression of TGFβ/Smad signaling in vitro is critical to maintaining characteristic features of mouse LECs, especially expression of the key transcription factors c-Maf and Prox1.
format article
author Dong Wang
Eddie Wang
Kelsey Liu
Chun-hong Xia
Song Li
Xiaohua Gong
author_facet Dong Wang
Eddie Wang
Kelsey Liu
Chun-hong Xia
Song Li
Xiaohua Gong
author_sort Dong Wang
title Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro
title_short Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro
title_full Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro
title_fullStr Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro
title_full_unstemmed Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro
title_sort roles of tgfβ and fgf signals during growth and differentiation of mouse lens epithelial cell in vitro
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/2f183bf36d2643e7a4bf43af4296f009
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AT kelseyliu rolesoftgfbandfgfsignalsduringgrowthanddifferentiationofmouselensepithelialcellinvitro
AT chunhongxia rolesoftgfbandfgfsignalsduringgrowthanddifferentiationofmouselensepithelialcellinvitro
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