MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens

Fibrotic cataracts have been attributed to transforming growth factor-beta (TGF-β)-induced epithelial-to-mesenchymal transition (EMT). Using mouse knockout (KO) models, our laboratory has identified MMP9 as a crucial protein in the TGF-β-induced EMT process. In this study, we further revealed an abs...

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Autores principales:	Zi Zhen (Ginny) Liu, Aftab Taiyab, Judith A. West-Mays
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	EMT MMP9 TGF-β lens PCO actin Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/280609783340456ba2978db6d68b59bb
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spelling	oai:doaj.org-article:280609783340456ba2978db6d68b59bb2021-11-11T17:24:29ZMMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens10.3390/ijms2221119881422-00671661-6596https://doaj.org/article/280609783340456ba2978db6d68b59bb2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11988https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Fibrotic cataracts have been attributed to transforming growth factor-beta (TGF-β)-induced epithelial-to-mesenchymal transition (EMT). Using mouse knockout (KO) models, our laboratory has identified MMP9 as a crucial protein in the TGF-β-induced EMT process. In this study, we further revealed an absence of alpha-smooth muscle actin (αSMA) and filamentous-actin (F-actin) stress fibers in MMP9KO mouse lens epithelial cell explants (LECs). Expression analysis using NanoString revealed no marked differences in αSMA (<i>ACTA2</i>) and beta-actin (β-actin) (<i>ACTB</i>) mRNA between the lenses of TGF-β-overexpressing (TGF-βtg) mice and TGF-βtg mice on a MMP9KO background. We subsequently conducted a protein array that revealed differential regulation of proteins known to be involved in actin polymerization and cell migration in TGF-β-treated MMP9KO mouse LECs when compared to untreated controls. Immunofluorescence analyses using rat LECs and the novel MMP9-specific inhibitor, JNJ0966, revealed similar differential regulation of cortactin, FAK, LIMK1 and MLC2 as observed in the array. Finally, a reduction in the nuclear localization of MRTF-A, a master regulator of cytoskeletal remodeling during EMT, was observed in rat LECs co-treated with JNJ0966 and TGF-β. In conclusion, MMP9 deficiency results in differential regulation of proteins involved in actin polymerization and cell migration, and this in turn prevents TGF-β-induced EMT in the lens.Zi Zhen (Ginny) LiuAftab TaiyabJudith A. West-MaysMDPI AGarticleEMTMMP9TGF-βlensPCOactinBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11988, p 11988 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EMT MMP9 TGF-β lens PCO actin Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	EMT MMP9 TGF-β lens PCO actin Biology (General) QH301-705.5 Chemistry QD1-999 Zi Zhen (Ginny) Liu Aftab Taiyab Judith A. West-Mays MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens
description	Fibrotic cataracts have been attributed to transforming growth factor-beta (TGF-β)-induced epithelial-to-mesenchymal transition (EMT). Using mouse knockout (KO) models, our laboratory has identified MMP9 as a crucial protein in the TGF-β-induced EMT process. In this study, we further revealed an absence of alpha-smooth muscle actin (αSMA) and filamentous-actin (F-actin) stress fibers in MMP9KO mouse lens epithelial cell explants (LECs). Expression analysis using NanoString revealed no marked differences in αSMA (<i>ACTA2</i>) and beta-actin (β-actin) (<i>ACTB</i>) mRNA between the lenses of TGF-β-overexpressing (TGF-βtg) mice and TGF-βtg mice on a MMP9KO background. We subsequently conducted a protein array that revealed differential regulation of proteins known to be involved in actin polymerization and cell migration in TGF-β-treated MMP9KO mouse LECs when compared to untreated controls. Immunofluorescence analyses using rat LECs and the novel MMP9-specific inhibitor, JNJ0966, revealed similar differential regulation of cortactin, FAK, LIMK1 and MLC2 as observed in the array. Finally, a reduction in the nuclear localization of MRTF-A, a master regulator of cytoskeletal remodeling during EMT, was observed in rat LECs co-treated with JNJ0966 and TGF-β. In conclusion, MMP9 deficiency results in differential regulation of proteins involved in actin polymerization and cell migration, and this in turn prevents TGF-β-induced EMT in the lens.
format	article
author	Zi Zhen (Ginny) Liu Aftab Taiyab Judith A. West-Mays
author_facet	Zi Zhen (Ginny) Liu Aftab Taiyab Judith A. West-Mays
author_sort	Zi Zhen (Ginny) Liu
title	MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens
title_short	MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens
title_full	MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens
title_fullStr	MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens
title_full_unstemmed	MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens
title_sort	mmp9 differentially regulates proteins involved in actin polymerization and cell migration during tgf-β-induced emt in the lens
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/280609783340456ba2978db6d68b59bb
work_keys_str_mv	AT zizhenginnyliu mmp9differentiallyregulatesproteinsinvolvedinactinpolymerizationandcellmigrationduringtgfbinducedemtinthelens AT aftabtaiyab mmp9differentiallyregulatesproteinsinvolvedinactinpolymerizationandcellmigrationduringtgfbinducedemtinthelens AT judithawestmays mmp9differentiallyregulatesproteinsinvolvedinactinpolymerizationandcellmigrationduringtgfbinducedemtinthelens
_version_	1718432107171151872

MMP9 Differentially Regulates Proteins Involved in Actin Polymerization and Cell Migration during TGF-β-Induced EMT in the Lens

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