1
40
2
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
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n/a
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
1880-1892
Issue
204
Volume
16
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Locate full-text within NEOMED Library's e-journal collections
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Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Suppression of transforming growth factor-beta effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor
Publisher
An entity responsible for making the resource available
Molecular Vision
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-09
Subject
The topic of the resource
anti-scarring agent; Biochemistry & Molecular Biology; choroidal; extracellular-matrix; fibrosis; glaucoma; identification; in-vivo; mitomycin-c; neovascularization; Ophthalmology; Surgery; tgf-beta
Creator
An entity primarily responsible for making the resource
Sapitro J; Dunmire J J; Scott S E; Sutariya V; Geldenhuys W J; Hewit M; Yue Byjt; Nakamura H
Description
An account of the resource
Purpose: Transforming growth factor-beta (TGF-beta) activity has been implicated in subconjunctival scarring in eyes following glaucoma filtration surgery (GFS). The purpose of this study is to determine whether an inhibitor for activin receptor-like kinase (ALK) 5 (also known as TGF-beta receptor type I) could suppress TGF-beta activity and thereby promote filtering bleb survival after GFS in a rabbit model. Methods: An ALK-5 inhibitor, SB-505124, was used. A docking study was performed to investigate the interaction between the inhibitor and the receptor. Immunofluorescence for connective tissue growth factor (CTGF) and alpha-smooth muscle actin (alpha-SMA) was performed in cultured rabbit subconjunctival fibroblasts. Immunoblotting for phosphorylated Smad2 (pSmad2), CTGF, and alpha-SMA was also performed. In an in vivo rabbit GFS model, SB-505124 was delivered in a lactose tablet during surgery. Eyes were examined by slit-lamp and intraocular pressure (IOP) was measured until the time of bleb failure or up to 28 days after surgery. Tissue sections on day 5 after surgery were histologically evaluated after staining with hematoxylin and eosin. The sections were also immunostained for CTGF and alpha-SMA. In addition, cell outgrowth from dissected subconjunctival tissues placed in a cell culture flask with media was investigated. Results: The docking study indicated hydrogen bond interactions between SB-505124 and amino acids His-283 and Ser-280 ALK-5. Suppression of pSmad2, CTGF, and alpha-SMA by SB-505124 was observed in cultured fibroblasts. Filtering blebs in the GFS with SB-505124 group were maintained for more than 10 days, and the period of bleb survival was significantly longer than that in controls. IOP levels after surgery seemed to be related to bleb survival. Histologically, subconjunctival cell infiltration and scarring at the surgical site in the GFS with SB-505124 and mitomycin C (MMC) groups were much subsided compared to controls. Suppression of CTGF and alpha-SMA by SB-505124 was also observed by immunofluorescence. Cell outgrowth from explants dissected from eyes to which SB-505124 was applied during GFS was robust while outgrowth was poor from those treated with MMC. Conclusions: The ALK-5 inhibitor SB-505124 was efficacious both in vitro and in vivo in suppressing the TGF-beta action. The inhibitor may provide a novel therapy for preventing ocular inflammation and scarring.
Identifier
An unambiguous reference to the resource within a given context
n/a
Format
The file format, physical medium, or dimensions of the resource
Journal Article
2010
anti-scarring agent
Biochemistry & Molecular Biology
choroidal
Dunmire J J
extracellular-matrix
Fibrosis
Geldenhuys W J
Glaucoma
Hewit M
identification
in-vivo
Journal Article
mitomycin-c
Molecular Vision
Nakamura H
Neovascularization
Ophthalmology
Sapitro J
Scott S E
Surgery
Sutariya V
tgf-beta
Yue Byjt
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1172/jci75331" target="_blank" rel="noreferrer noopener">http://doi.org/10.1172/jci75331</a>
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
5225-5238
Issue
12
Volume
124
Search for Full-text
Locate full-text within NEOMED Library's e-journal collections
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice
Publisher
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Journal of Clinical Investigation
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-12
Subject
The topic of the resource
activation; cation channel trpv4; contraction; disease; fibroblasts; gene-expression; induced lung injury; mechanisms; pathogenesis; Research & Experimental Medicine; tgf-beta
Creator
An entity primarily responsible for making the resource
Rahaman S O; Grove L M; Paruchuri S; Southern B D; Abraham S; Niese K A; Scheraga R G; Ghosh S; Thodeti C K; Zhang D X; Moran M M; Schilling W R; Tschumperlin D J; Olman M A
Description
An account of the resource
Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disorder with no effective medical treatments available. The generation of myofibroblasts, which are critical for fibrogenesis, requires both a mechanical signal and activated TGF-beta; however, it is not clear how fibroblasts sense and transmit the mechanical signal(s) that promote differentiation into myofibroblasts. As transient receptor potential vanilloid 4 (TRPV4) channels are activated in response to changes in plasma membrane stretch/matrix stiffness, we investigated whether TRPV4 contributes to generation of myofibroblasts and/or experimental lung fibrosis. We determined that TRPV4 activity is upregulated in lung fibroblasts derived from patients with IPF. Moreover, TRPV4-deficient mice were protected from fibrosis. Furthermore, genetic ablation or pharmacological inhibition of TRPV4 function abrogated myofibroblast differentiation, which was restored by TRPV4 reintroduction. TRPV4 channel activity was elevated when cells were plated on matrices of increasing stiffness or on fibrotic lung tissue, and matrix stiffness-dependent myofibroblast differentiation was reduced in response to TRVP4 inhibition. TRPV4 activity modulated TGF-beta 1-dependent actions in a SMAD-independent manner, enhanced actomyosin remodeling, and increased nuclear translocation of the alpha-SMA transcription coactivator (MRTF-A). Together, these data indicate that TRPV4 activity mediates pulmonary fibrogenesis and suggest that manipulation of TRPV4 channel activity has potential as a therapeutic approach for fibrotic diseases.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1172/jci75331" target="_blank" rel="noreferrer noopener">10.1172/jci75331</a>
Format
The file format, physical medium, or dimensions of the resource
Journal Article
2014
Abraham S
activation
cation channel trpv4
contraction
Department of Family & Community Medicine
Disease
fibroblasts
gene-expression
Ghosh S
Grove L M
induced lung injury
Journal Article
Journal of Clinical Investigation
mechanisms
Moran M M
NEOMED College of Medicine
Niese K A
Olman M A
Paruchuri S
Pathogenesis
Rahaman S O
Research & Experimental Medicine
Scheraga R G
Schilling W R
Southern B D
tgf-beta
Thodeti C K
Tschumperlin D J
Zhang D X