Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells

ABSTRACT Long‐term steroid use, though essential for treating eye diseases, can cause increased intraocular pressure (IOP) in susceptible individuals and may lead to steroid‐induced glaucoma in a subset of patients. This study investigated the effect of bone morphogenetic protein‐7 (BMP‐7) on steroi...

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Main Authors: Eun Woo Kim, Jin‐Ok Choi, Min Kyung Chae, Jin‐Sol Lee, Chang Ha Lee, Jo Eun Um, Nam Hee Kim, Jihyeong Kim, Wungrak Choi, Chan Yun Kim
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:FASEB BioAdvances
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Online Access:https://doi.org/10.1096/fba.2025-00080
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author Eun Woo Kim
Jin‐Ok Choi
Min Kyung Chae
Jin‐Sol Lee
Chang Ha Lee
Jo Eun Um
Nam Hee Kim
Jihyeong Kim
Wungrak Choi
Chan Yun Kim
author_facet Eun Woo Kim
Jin‐Ok Choi
Min Kyung Chae
Jin‐Sol Lee
Chang Ha Lee
Jo Eun Um
Nam Hee Kim
Jihyeong Kim
Wungrak Choi
Chan Yun Kim
author_sort Eun Woo Kim
collection DOAJ
description ABSTRACT Long‐term steroid use, though essential for treating eye diseases, can cause increased intraocular pressure (IOP) in susceptible individuals and may lead to steroid‐induced glaucoma in a subset of patients. This study investigated the effect of bone morphogenetic protein‐7 (BMP‐7) on steroid‐induced extracellular matrix (ECM) synthesis in human trabecular meshwork (TM) cells. We sought to explore the potential of BMP‐7 as a protective agent against steroid‐induced ECM accumulation in the TM. Human TM cells (HTMCs) were treated with either steroids alone or a combination of steroids and BMP‐7 to compare their effects on ECM production. BMP‐7, known for its transforming growth factor beta (TGF‐β) antagonistic properties, was administered using a micellized protein transduction domain (mPTD)‐fused BMP‐7 polypeptide to enhance activity. Gene expression analysis was conducted to identify specific genes involved in ECM regulation. BMP‐7 effectively inhibited steroid‐induced ECM accumulation in HTMCs. There was a significant reduction in ECM production in the steroid and BMP‐7 co‐treated group compared with that in the steroid‐only group. Furthermore, several genes involved in ECM regulation were identified in the co‐treatment, underscoring BMP‐7's potential role in modulating ECM metabolism. These findings demonstrate that BMP‐7 exerts protective, anti‐fibrotic effects in HTMCs by inhibiting steroid‐induced ECM synthesis. BMP‐7 may serve as a promising therapeutic target for preventing or treating steroid‐induced glaucoma by maintaining normal aqueous humor outflow and preventing IOP elevation.
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spelling doaj-art-ddc864e5c50f4ee7950c86e2fc5f61a92025-08-20T02:08:36ZengWileyFASEB BioAdvances2573-98322025-06-0176n/an/a10.1096/fba.2025-00080Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork CellsEun Woo Kim0Jin‐Ok Choi1Min Kyung Chae2Jin‐Sol Lee3Chang Ha Lee4Jo Eun Um5Nam Hee Kim6Jihyeong Kim7Wungrak Choi8Chan Yun Kim9Department of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaDivision of AI and Data Analysis Neurogrin Inc. Seoul Republic of KoreaDepartment of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaMET Life Science Seoul Republic of KoreaOral Cancer Research Institute Yonsei University College of Dentistry Seoul Republic of KoreaDepartment of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaDepartment of Ophthalmology, Institute of Vision Research Yonsei University College of Medicine Seoul Republic of KoreaABSTRACT Long‐term steroid use, though essential for treating eye diseases, can cause increased intraocular pressure (IOP) in susceptible individuals and may lead to steroid‐induced glaucoma in a subset of patients. This study investigated the effect of bone morphogenetic protein‐7 (BMP‐7) on steroid‐induced extracellular matrix (ECM) synthesis in human trabecular meshwork (TM) cells. We sought to explore the potential of BMP‐7 as a protective agent against steroid‐induced ECM accumulation in the TM. Human TM cells (HTMCs) were treated with either steroids alone or a combination of steroids and BMP‐7 to compare their effects on ECM production. BMP‐7, known for its transforming growth factor beta (TGF‐β) antagonistic properties, was administered using a micellized protein transduction domain (mPTD)‐fused BMP‐7 polypeptide to enhance activity. Gene expression analysis was conducted to identify specific genes involved in ECM regulation. BMP‐7 effectively inhibited steroid‐induced ECM accumulation in HTMCs. There was a significant reduction in ECM production in the steroid and BMP‐7 co‐treated group compared with that in the steroid‐only group. Furthermore, several genes involved in ECM regulation were identified in the co‐treatment, underscoring BMP‐7's potential role in modulating ECM metabolism. These findings demonstrate that BMP‐7 exerts protective, anti‐fibrotic effects in HTMCs by inhibiting steroid‐induced ECM synthesis. BMP‐7 may serve as a promising therapeutic target for preventing or treating steroid‐induced glaucoma by maintaining normal aqueous humor outflow and preventing IOP elevation.https://doi.org/10.1096/fba.2025-00080bone morphogenetic protein‐7extracellular matrixfibrosisglaucomasteroidtrabecular meshwork
spellingShingle Eun Woo Kim
Jin‐Ok Choi
Min Kyung Chae
Jin‐Sol Lee
Chang Ha Lee
Jo Eun Um
Nam Hee Kim
Jihyeong Kim
Wungrak Choi
Chan Yun Kim
Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells
FASEB BioAdvances
bone morphogenetic protein‐7
extracellular matrix
fibrosis
glaucoma
steroid
trabecular meshwork
title Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells
title_full Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells
title_fullStr Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells
title_full_unstemmed Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells
title_short Effects of Bone Morphogenetic Protein‐7 on Steroid‐Induced Extracellular Matrix Accumulation in Human Trabecular Meshwork Cells
title_sort effects of bone morphogenetic protein 7 on steroid induced extracellular matrix accumulation in human trabecular meshwork cells
topic bone morphogenetic protein‐7
extracellular matrix
fibrosis
glaucoma
steroid
trabecular meshwork
url https://doi.org/10.1096/fba.2025-00080
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