mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells

Abstract We examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-β2) in cultured human trabecular meshwork (hTM) cells. TGF-β2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (αSMA)...

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Main Authors: Nozomi Igarashi, Megumi Honjo, Makoto Aihara
Format: Article
Language:English
Published: Nature Portfolio 2021-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-93580-3
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author Nozomi Igarashi
Megumi Honjo
Makoto Aihara
author_facet Nozomi Igarashi
Megumi Honjo
Makoto Aihara
author_sort Nozomi Igarashi
collection DOAJ
description Abstract We examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-β2) in cultured human trabecular meshwork (hTM) cells. TGF-β2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (αSMA) in hTM cells was examined in the presence or absence of mTOR inhibitors using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The migration rates of hTM cells were examined in the presence of TGF-β2 with or without mTOR inhibitors. An in vitro study showed that the expression of fibronectin, COL1A1, and αSMA was upregulated by TGF-β2 treatment of hTM cells; such upregulation was significantly suppressed by mTOR inhibitors. The inhibitors significantly reduced the migration rate of TGF-β2-stimulated hTM cells. mTOR inhibitors may usefully reduce the fibrotic response of hTM cells and we may have to explore if it is also effective in in vivo model.
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spelling doaj.art-0d72df1cb3494545b07a52c213b766672022-12-21T20:36:29ZengNature PortfolioScientific Reports2045-23222021-07-0111111010.1038/s41598-021-93580-3mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cellsNozomi Igarashi0Megumi Honjo1Makoto Aihara2Department of Ophthalmology, Graduate School of Medicine, The University of TokyoDepartment of Ophthalmology, Graduate School of Medicine, The University of TokyoDepartment of Ophthalmology, Graduate School of Medicine, The University of TokyoAbstract We examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-β2) in cultured human trabecular meshwork (hTM) cells. TGF-β2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (αSMA) in hTM cells was examined in the presence or absence of mTOR inhibitors using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The migration rates of hTM cells were examined in the presence of TGF-β2 with or without mTOR inhibitors. An in vitro study showed that the expression of fibronectin, COL1A1, and αSMA was upregulated by TGF-β2 treatment of hTM cells; such upregulation was significantly suppressed by mTOR inhibitors. The inhibitors significantly reduced the migration rate of TGF-β2-stimulated hTM cells. mTOR inhibitors may usefully reduce the fibrotic response of hTM cells and we may have to explore if it is also effective in in vivo model.https://doi.org/10.1038/s41598-021-93580-3
spellingShingle Nozomi Igarashi
Megumi Honjo
Makoto Aihara
mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells
Scientific Reports
title mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells
title_full mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells
title_fullStr mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells
title_full_unstemmed mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells
title_short mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells
title_sort mtor inhibitors potentially reduce tgf β2 induced fibrogenic changes in trabecular meshwork cells
url https://doi.org/10.1038/s41598-021-93580-3
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AT makotoaihara mtorinhibitorspotentiallyreducetgfb2inducedfibrogenicchangesintrabecularmeshworkcells