Activation of valvular interstitial cells is mediated by transforming growth factor-β1 interactions with matrix molecules

Cushing, Melinda C.; Liao, Jo-Tsu; Anseth, Kristi S.

doi:10.1016/j.matbio.2005.06.007

Cited by 102 publications

(100 citation statements)

References 36 publications

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“…19 TGF-␤1 activation has also been shown to be integrin-mediated in vivo. 61 We previously report the upregulation of fibronectin, changes in ␣v␤6 integrin, and prominent fibrillar adhesion assembly by VICs at the WE.…”

Section: Discussionmentioning

confidence: 99%

“…It is secreted by numerous cell types 17 including VICs with potent autocrine effects. 18,19 It is known to promote differentiation of mesenchymal cells into myofibroblasts 20,21 and to regulate multiple aspects of the myofibroblast phenotype through transcriptional activation of ␣-SMA, collagen, 22 matrix metalloproteinases, 23 and other cytokines such as connective tissue growth factor 24 and basic fibroblast growth factor. [25][26][27] TGF-␤ is present in mitral valve prolapse 6,28 and calcific aortic stenosis.…”

mentioning

confidence: 99%

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Transforming Growth Factor-β Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells

Liu

Gotlieb

2008

The American Journal of Pathology

100

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The regulation of valve interstitial cell (VIC) function in response to tissue injury and valve disease is not well understood. Because transforming growth factor-␤ (TGF-␤) has been implicated in tissue repair, we tested the hypothesis that TGF-␤ is a regulator of VIC activation and associated cell responses that occur during early repair processes. We used a well-characterized wound model that was created by mechanical denudation of a confluent VIC monolayer to study activation and repair 24 hours after wounding. VIC activation was demonstrated by immunofluorescent localization of ␣-smooth muscle actin (␣-SMA), and ␣-SMA mRNA levels were quantified by real-time polymerase chain reaction. Proliferation and apoptosis were quantified by bromodeoxyuridine staining and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Repair was quantified by measuring VIC extension into the wound , and TGF-␤ expression was shown by immunofluorescent localization of intracellular TGF-␤. Compared with nonwounded monolayers, VICs at the wound edge showed ␣-SMA staining, increased ␣-SMA mRNA content, elongation into the wound with stress fibers, proliferation, and apoptosis. VICs at the wound edge also showed increased TGF-␤ and pSmad2/3 staining with co-expression of ␣-SMA. Addition of TGF-␤ neutralizing antibody to the wound decreased VIC activation, ␣-SMA mRNA content, proliferation, apoptosis, wound closure rate, and stress fibers. Conversely, exogenous addition of TGF-␤ to the wound increased VIC activation , proliferation , wound closure rate , and stress fibers. Thus , wounding activates VICs , and TGF-␤ signaling modulates VIC response to injury.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Transforming Growth Factor-β Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells

Liu

Gotlieb

2008

The American Journal of Pathology

100

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“…However, microspheres, when used alone, often coalesce or migrate, which may not allow the controlled spatial delivery. In tissue engineering, it is desirable to controlled release biological molecules within the scaffold [2,3,[129][130][131][132][133][134]. Biological factors have been directly added into a polymer solution or emulsion to fabricate scaffolds [135,136].…”

Section: Bioactive Molecule Deliverymentioning

confidence: 99%

Biomimetic materials for tissue engineering

Peter

2008

Advanced Drug Delivery Reviews

1,213

819

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Tissue engineering and regenerative medicine is an exciting research area that aims at regenerative alternatives to harvested tissues for transplantation. Biomaterials play a pivotal role as scaffolds to provide three-dimensional templates and synthetic extracellular-matrix environments for tissue regeneration. It is often beneficial for the scaffolds to mimic certain advantageous characteristics of the natural extracellular matrix, or developmental or would healing programs. This article reviews current biomimetic materials approaches in tissue engineering. These include synthesis to achieve certain compositions or properties similar to those of the extracellular matrix, novel processing technologies to achieve structural features mimicking the extracellular matrix on various levels, approaches to emulate cell-extracellular matrix interactions, and biologic delivery strategies to recapitulate a signaling cascade or developmental/would-healing program. The article also provides examples of enhanced cellular/tissue functions and regenerative outcomes, demonstrating the excitement and significance of the biomimetic materials for tissue engineering and regeneration.

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“…Stiffer substrates such as polystyrene promote VIC calcification whereas collagen, hyaluronan, and fibronectin gels or surface coatings reduce calcification [11][12][13]. Production of calcific nodules by VICs is a complicated process, however, involving multiple cell signaling pathways that are influenced by inflammatory factors, growth factors such as TGF-β, substrate stiffness, biological activity of the substrate, and oxygen and nutrient availability [12][13][14][15][16][17]. 2D culture systems, such as bioactive surface coatings on tissue culture polystyrene, have been used to successfully isolate many of these factors for analysis but yield limited results when used to replicate the complex array of factors involved in CAVD.…”

Section: Introductionmentioning

confidence: 99%

Multilayer three-dimensional filter paper constructs for the culture and analysis of aortic valvular interstitial cells

et al. 2015

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Culturing aortic valvular interstitial cells in an environment that models the aortic valve is an essential step towards understanding the progression of calcific aortic valve disease. Here the adaption of a 3D stacked paper-based culture system is presented for analyzing valve cells in a thick collagen gel matrix. Filter paper layers, modeled after a 96-well plate design, were printed with a wax well-plate template and then seeded with valve cell and collagen mixtures that quickly gelled into 3D cultures. Stacking these layers permitted extensive customization of culture thickness and cell density profiles to model the full thickness of native valve tissue.

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Activation of valvular interstitial cells is mediated by transforming growth factor-β1 interactions with matrix molecules

Cited by 102 publications

References 36 publications

Transforming Growth Factor-β Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells

Transforming Growth Factor-β Regulates in Vitro Heart Valve Repair by Activated Valve Interstitial Cells

Biomimetic materials for tissue engineering

Multilayer three-dimensional filter paper constructs for the culture and analysis of aortic valvular interstitial cells

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