Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells

Abstract The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregul...

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Autores principales:	Yuan Zhang, Scheffer C. G. Tseng, Ying-Ting Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3409cb0c93944b94823b846cd959cff4
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spelling	oai:doaj.org-article:3409cb0c93944b94823b846cd959cff42021-12-02T13:26:24ZSuppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells10.1038/s41598-021-86591-72045-2322https://doaj.org/article/3409cb0c93944b94823b846cd959cff42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86591-7https://doaj.org/toc/2045-2322Abstract The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregulated by dexamethasone. Continuous passage of these cells on 2D Matrigel resulted in a gradual loss of expression of these markers. However, such a loss was restored by seeding cells in 3D Matrigel where expression of TM markers was further upregulated upon continuous passage. In contrast, TM cells seeded on fibronectin, collagen I/IV, or laminin lost expression of these markers and turned into myofibroblasts with expression of αSMA, which were dose-dependently upregulated by TGF-β1/TGF-β2. TM cells in 3D Matrigel also expressed TGF-β1/TGF-β3 despite challenge of TGF-β1. The maintenance of TM phenotype by 3D Matrigel was linked to inhibition of canonical TGF-β signaling and activation of pFAK-pSrc-pP190RhoGAP-P120RasGAP signaling. These findings indicate that basement membrane matrix with low rigidity plays an active role in maintaining TM phenotype in the presence of TGF-β1 and shed light on its physiological role. Furthermore, abnormal matrices may perpetuate the pathological TM phenotype when the level of TGF-β2 is elevated in glaucoma patients.Yuan ZhangScheffer C. G. TsengYing-Ting ZhuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuan Zhang Scheffer C. G. Tseng Ying-Ting Zhu Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
description	Abstract The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregulated by dexamethasone. Continuous passage of these cells on 2D Matrigel resulted in a gradual loss of expression of these markers. However, such a loss was restored by seeding cells in 3D Matrigel where expression of TM markers was further upregulated upon continuous passage. In contrast, TM cells seeded on fibronectin, collagen I/IV, or laminin lost expression of these markers and turned into myofibroblasts with expression of αSMA, which were dose-dependently upregulated by TGF-β1/TGF-β2. TM cells in 3D Matrigel also expressed TGF-β1/TGF-β3 despite challenge of TGF-β1. The maintenance of TM phenotype by 3D Matrigel was linked to inhibition of canonical TGF-β signaling and activation of pFAK-pSrc-pP190RhoGAP-P120RasGAP signaling. These findings indicate that basement membrane matrix with low rigidity plays an active role in maintaining TM phenotype in the presence of TGF-β1 and shed light on its physiological role. Furthermore, abnormal matrices may perpetuate the pathological TM phenotype when the level of TGF-β2 is elevated in glaucoma patients.
format	article
author	Yuan Zhang Scheffer C. G. Tseng Ying-Ting Zhu
author_facet	Yuan Zhang Scheffer C. G. Tseng Ying-Ting Zhu
author_sort	Yuan Zhang
title	Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
title_short	Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
title_full	Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
title_fullStr	Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
title_full_unstemmed	Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
title_sort	suppression of tgf-β1 signaling by matrigel via fak signaling in cultured human trabecular meshwork cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3409cb0c93944b94823b846cd959cff4
work_keys_str_mv	AT yuanzhang suppressionoftgfb1signalingbymatrigelviafaksignalinginculturedhumantrabecularmeshworkcells AT scheffercgtseng suppressionoftgfb1signalingbymatrigelviafaksignalinginculturedhumantrabecularmeshworkcells AT yingtingzhu suppressionoftgfb1signalingbymatrigelviafaksignalinginculturedhumantrabecularmeshworkcells
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Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells

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