Microdeformation of Three-Dimensional Cultured Fibroblasts Induces Gene Expression and Morphological Changes

Lu, Feng; Ogawa, Rei; Nguyen, Dinh Thi; Chen, Bin; Guo, Dongyun; Helm, Douglas L.; Zhan, Qian; Murphy, Gëorge F.; Orgill, Dennis P.

doi:10.1097/sap.0b013e3181ea1e9b

Cited by 73 publications

(75 citation statements)

References 21 publications

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“…This is because although GAB1 has been considered a major player for mediating the activation of the PI3K/AKT1 pathway by FGF via FGFRs [8,12,13], little is known regarding the proximal FGF/FGFR signaling mechanism that controls activation of the PI3K/AKT1 pathway. Our findings suggest that caveolae functions as a focal center for organizing the proximal FGF2/FGFR1 signaling via FRS2a in placental endothelial cells because: 1) FRS2a has a caveolin binding motif ( 65 YGYDSNLF 72 , aromatic amino acids underlined) [38] that is highly conserved among different species [40][41][42]; 2)…”

Section: Discussionmentioning

confidence: 99%

Compartmentalizing Proximal FGFR1 Signaling in Ovine Placental Artery Endothelial Cell Caveolae1

Feng¹,

Zhang²,

Wang³

et al. 2012

Biology of Reproduction

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Caveolae orchestrate the dominant placental angiogenic growth factor fibroblast growth factor 2 (FGF2) signaling primarily via FGF receptor 1 (FGFR1) in placental artery endothelial cells; however, how the proximal FGF2/FGFR1 signaling is organized in the caveolae is obscure. We have shown in the present study that the FGFR substrate 2alpha (FRS2alpha) is physically associated with FGFR1, and both are targeted to the caveolae via interaction with caveolin-1 in ovine fetoplacental artery endothelial cells. Treatment with FGF2 rapidly stimulated time- and concentration-dependent FRS2alpha tyrosine phosphorylation and recruited the cytosolic growth factor receptor-bound protein 2 (GRB2)-GRB2-associated binding protein 1 (GAB1) complex to the caveolae, where they formed a ternary complex with FRS2alpha. Disruption of caveolae by cholesterol depletion with methyl-beta-cyclodextrin inhibited FGF2-induced FRS2alpha tyrosine phosphorylation, and it blocked the FGF2-induced recruitment of GRB2 and GAB1 to the caveolae and formation of the FRS2alpha-GRB2-GAB1 complex in the caveolae, as well as activation of the PI3K/AKT1 and MAPK1/2 pathways. Thus, these findings have demonstrated that the proximal fibroblast growth factor (FGF2/FGFR1) signaling is compartmentalized in the placental endothelial caveolae via the FGFR substrate 2α that mediates formation of a FRS2α-GRB2-GAB1 complex.

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Section: Discussionmentioning

confidence: 99%

Compartmentalizing Proximal FGFR1 Signaling in Ovine Placental Artery Endothelial Cell Caveolae1

Feng¹,

Zhang²,

Wang³

et al. 2012

Biology of Reproduction

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“…We and others have shown that tension can markedly alter fibroblast expression of matrix remodeling and inflammatory genes (Kessler-Becker et al, 2004;Derderian et al, 2005). Moreover, mechanical forces can induce fibroblast collagen production, a-smooth muscle actin expression, cytokine expression, and proliferation in vitro (Yang et al, 2004;Webb et al, 2006;Hinz et al, 2007;Lu et al, 2011), suggesting that mechanical tension is largely driven by fibroblast-mediated mechanisms. Keratinocytes, which form the initial barrier to the external world, are also mechanically responsive and are important regulators of skin activity.…”

Section: Mechanosensing Cells Of the Skinmentioning

confidence: 96%

Pushing Back: Wound Mechanotransduction in Repair and Regeneration

Wong

Akaishi

Longaker

et al. 2011

Journal of Investigative Dermatology

183

161

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Human skin is a highly specialized mechanoresponsive interface separating our bodies from the external environment. It must constantly adapt to dynamic physical cues ranging from rapid expansion during embryonic and early postnatal development to ubiquitous external forces throughout life. Despite the suspected role of the physical environment in cutaneous processes, the fundamental molecular mechanisms responsible for how skin responds to force remain unclear. Intracellular pathways convert mechanical cues into biochemical responses (in a process known as mechanotransduction) via complex mechanoresponsive elements that often blur the distinction between physical and chemical signaling. For example, cellular focal adhesion components exhibit dual biochemical and scaffolding functions that are critically modulated by force. Moreover, the extracellular matrix itself is increasingly recognized to mechanically regulate the spatiotemporal distribution of soluble and matrix-bound ligands, underscoring the importance of bidirectional crosstalk between cells and their physical environment. It seems likely that a structural hierarchy exists to maintain both cells and matrix in mechanical homeostasis and that dysregulation of this architectural integrity may underlie or contribute to various skin disorders. An improved understanding of these interactions will facilitate the development of novel biophysical materials and mechanomodulatory approaches to augment wound repair and regeneration.

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“…Moreover, fibroblasts by regulating ECM homeostasis, control elasticity and strength of the tissue mechanical properties, that in turn influence fibroblast behavior. In 3D, such biochemical, mechanical and physical cues were also shown to be fundamental for sustaining cell homeostasis (Chiquet, 1999;Chiquet et al, 2003Chiquet et al, , 2009Farran et al, 2010;Hakkinen et al, 2011;Lu et al, 2011). The dynamic conditions as compared to the static ones creating a shear stress and/or fluid flow, can also regulate cell behavior either in 2D or in 3D (Kinney et al, 2011;Wang and Tarbell, 2000;Ng and Swartz, 2003;Shi and Tarbell, 2011).…”

Section: Discussionmentioning

confidence: 97%

Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

Montani

Steimberg

Boniotti

et al. 2014

Toxicology and Applied Pharmacology

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Microdeformation of Three-Dimensional Cultured Fibroblasts Induces Gene Expression and Morphological Changes

Abstract: Microdeformations produced by the combination of polyurethane foam and suction are associated with increased fibroblast proliferation and up-regulation of gene expressions in fibroblasts.

Cited by 73 publications

References 21 publications

Compartmentalizing Proximal FGFR1 Signaling in Ovine Placental Artery Endothelial Cell Caveolae1

Compartmentalizing Proximal FGFR1 Signaling in Ovine Placental Artery Endothelial Cell Caveolae1

Pushing Back: Wound Mechanotransduction in Repair and Regeneration

Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

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