Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions
Trabecular meshwork (TM) tissue is subjected to constant mechanical stress due to the ocular pulse created by the cardiac cycle. This brings about alterations in the membrane lipids and associated cell–cell adhesion and cell–extracellular matrix (ECM) interactions, triggering intracellular signaling...
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Frontiers Media S.A.
2022-09-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.874828/full |
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author | Avinash Soundararajan Ting Wang Ting Wang Rekha Sundararajan Aruna Wijeratne Aruna Wijeratne Amber Mosley Amber Mosley Amber Mosley Faith Christine Harvey Faith Christine Harvey Sanjoy Bhattacharya Sanjoy Bhattacharya Padmanabhan Paranji Pattabiraman Padmanabhan Paranji Pattabiraman Padmanabhan Paranji Pattabiraman |
author_facet | Avinash Soundararajan Ting Wang Ting Wang Rekha Sundararajan Aruna Wijeratne Aruna Wijeratne Amber Mosley Amber Mosley Amber Mosley Faith Christine Harvey Faith Christine Harvey Sanjoy Bhattacharya Sanjoy Bhattacharya Padmanabhan Paranji Pattabiraman Padmanabhan Paranji Pattabiraman Padmanabhan Paranji Pattabiraman |
author_sort | Avinash Soundararajan |
collection | DOAJ |
description | Trabecular meshwork (TM) tissue is subjected to constant mechanical stress due to the ocular pulse created by the cardiac cycle. This brings about alterations in the membrane lipids and associated cell–cell adhesion and cell–extracellular matrix (ECM) interactions, triggering intracellular signaling responses to counter mechanical insults. A loss of such response can lead to elevated intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma. This study is aimed to understand the changes in signaling responses by TM subjected to mechanical stretch. We utilized multiomics to perform an unbiased mRNA sequencing to identify changes in transcripts, mass spectrometry- (MS-) based quantitative proteomics for protein changes, and multiple reaction monitoring (MRM) profiling-based MS and high-performance liquid chromatography (HPLC-) based MS to characterize the lipid changes. We performed pathway analysis to obtain an integrated map of TM response to mechanical stretch. The human TM cells subjected to mechanical stretch demonstrated an upregulation of protein quality control, oxidative damage response, pro-autophagic signal, induction of anti-apoptotic, and survival signaling. We propose that mechanical stretch-induced lipid signaling via increased ceramide and sphingomyelin potentially contributes to increased TM stiffness through actin-cytoskeleton reorganization and profibrotic response. Interestingly, increased phospholipids and diacylglycerol due to mechanical stretch potentially enable cell membrane remodeling and changes in signaling pathways to alter cellular contractility. Overall, we propose the mechanistic interplay of macromolecules to bring about a concerted cellular response in TM cells to achieve mechanotransduction and IOP regulation when TM cells undergo mechanical stretch. |
first_indexed | 2024-04-12T04:42:28Z |
format | Article |
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institution | Directory Open Access Journal |
issn | 2296-634X |
language | English |
last_indexed | 2024-04-12T04:42:28Z |
publishDate | 2022-09-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cell and Developmental Biology |
spelling | doaj.art-bbeb5aba0963462db5155b43f86b1d5a2022-12-22T03:47:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-09-011010.3389/fcell.2022.874828874828Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactionsAvinash Soundararajan0Ting Wang1Ting Wang2Rekha Sundararajan3Aruna Wijeratne4Aruna Wijeratne5Amber Mosley6Amber Mosley7Amber Mosley8Faith Christine Harvey9Faith Christine Harvey10Sanjoy Bhattacharya11Sanjoy Bhattacharya12Padmanabhan Paranji Pattabiraman13Padmanabhan Paranji Pattabiraman14Padmanabhan Paranji Pattabiraman15Department of Ophthalmology, Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Ophthalmology, Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Ophthalmology, Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United StatesCenter for Proteome Analysis, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United StatesCenter for Proteome Analysis, Indiana University School of Medicine, Indianapolis, IN, United StatesCenter for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, United StatesBascom Palmer Eye Institute, Miller School of Medicine at University of Miami, Miami, FL, United StatesMiami Integrative Metabolomics Research Center, Miami, FL, United StatesBascom Palmer Eye Institute, Miller School of Medicine at University of Miami, Miami, FL, United StatesMiami Integrative Metabolomics Research Center, Miami, FL, United StatesDepartment of Ophthalmology, Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesStark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United StatesTrabecular meshwork (TM) tissue is subjected to constant mechanical stress due to the ocular pulse created by the cardiac cycle. This brings about alterations in the membrane lipids and associated cell–cell adhesion and cell–extracellular matrix (ECM) interactions, triggering intracellular signaling responses to counter mechanical insults. A loss of such response can lead to elevated intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma. This study is aimed to understand the changes in signaling responses by TM subjected to mechanical stretch. We utilized multiomics to perform an unbiased mRNA sequencing to identify changes in transcripts, mass spectrometry- (MS-) based quantitative proteomics for protein changes, and multiple reaction monitoring (MRM) profiling-based MS and high-performance liquid chromatography (HPLC-) based MS to characterize the lipid changes. We performed pathway analysis to obtain an integrated map of TM response to mechanical stretch. The human TM cells subjected to mechanical stretch demonstrated an upregulation of protein quality control, oxidative damage response, pro-autophagic signal, induction of anti-apoptotic, and survival signaling. We propose that mechanical stretch-induced lipid signaling via increased ceramide and sphingomyelin potentially contributes to increased TM stiffness through actin-cytoskeleton reorganization and profibrotic response. Interestingly, increased phospholipids and diacylglycerol due to mechanical stretch potentially enable cell membrane remodeling and changes in signaling pathways to alter cellular contractility. Overall, we propose the mechanistic interplay of macromolecules to bring about a concerted cellular response in TM cells to achieve mechanotransduction and IOP regulation when TM cells undergo mechanical stretch.https://www.frontiersin.org/articles/10.3389/fcell.2022.874828/fulltrabecular meshwork (TM)glaucomaocular hypertensionmechanical stretchmultiomics analysiscytoskeleton |
spellingShingle | Avinash Soundararajan Ting Wang Ting Wang Rekha Sundararajan Aruna Wijeratne Aruna Wijeratne Amber Mosley Amber Mosley Amber Mosley Faith Christine Harvey Faith Christine Harvey Sanjoy Bhattacharya Sanjoy Bhattacharya Padmanabhan Paranji Pattabiraman Padmanabhan Paranji Pattabiraman Padmanabhan Paranji Pattabiraman Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions Frontiers in Cell and Developmental Biology trabecular meshwork (TM) glaucoma ocular hypertension mechanical stretch multiomics analysis cytoskeleton |
title | Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions |
title_full | Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions |
title_fullStr | Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions |
title_full_unstemmed | Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions |
title_short | Multiomics analysis reveals the mechanical stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions |
title_sort | multiomics analysis reveals the mechanical stress dependent changes in trabecular meshwork cytoskeletal extracellular matrix interactions |
topic | trabecular meshwork (TM) glaucoma ocular hypertension mechanical stretch multiomics analysis cytoskeleton |
url | https://www.frontiersin.org/articles/10.3389/fcell.2022.874828/full |
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