Mechanical Load Enhances Procollagen Processing in Dermal Fibroblasts by Regulating Levels of Procollagen C-Proteinase

Parsons, Maddy; Kessler, Efrat; Guy, Laurent; Brown, Rachel; Bishop, June E.

doi:10.1006/excr.1999.4618

Cited by 80 publications

(55 citation statements)

References 33 publications

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“…The effect of mechanical stress on the changes in proteosynthetic activity has been observed in human fibroblast cultures growing on a collagen lattice. A mechanical load enhanced procollagen synthesis, insoluble collagen deposition, and the synthesis of procollagen mRNA and procollagen C-proteinase mRNA (Parsons et al, 1999). Changes in the matrix proteases MMP1, 2, and 3 and in the inhibitors TIMP1 and 2 have also been shown in relation to an altered orientation of fibroblasts due to mechanical forces (Mudera et al, 2000).…”

Section: Discussionmentioning

confidence: 96%

Reaction of the Skin Fibroblast Cytoskeleton to Micromanipulation Interventions

Veselská

Janisch

2001

Journal of Structural Biology

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Section: Discussionmentioning

confidence: 96%

Reaction of the Skin Fibroblast Cytoskeleton to Micromanipulation Interventions

Veselská

Janisch

2001

Journal of Structural Biology

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“…Intermittent cyclic stretch was applied to BPAEC as previously described (35). In brief, confluent Bioflex plates were placed on a Flexercell 3000 base plate in the incubator, and membranes at the bottom of the plates were subjected to a vacuum of Ϫ20 kPa at a frequency of 15 cycles/min for up to 6 h. During each cycle, cells were stretched for 3 s and relaxed for 1 s. A vacuum of Ϫ20 kPa was found to produce membrane strain of ϳ25% when the loading posts were installed beneath the wells.…”

Section: Methodsmentioning

confidence: 99%

Stretch-induced phosphorylation of focal adhesion kinase in endothelial cells: role of mitochondrial oxidants

Ali

Mungai

Schumacker

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical stretch activates a number of signaling pathways in endothelial cells, and it elicits a variety of functional responses including increases in the phosphorylation of focal adhesion kinase (FAK), a nonreceptor tyrosine kinase involved in integrin-mediated signal transduction. Stretch also triggers an increase in the generation of reactive oxygen species (ROS), which may function as second messengers in the signal transduction cascades that activate cellular responses to strain. Mitochondria represent an important source of ROS in the cell, and these organelles may release ROS in response to strain by virtue of their attachment to cytoskeletal proteins. We therefore tested whether cyclic stretch increases FAK phosphorylation at Tyr397 through a mitochondrial ROS signaling pathway in bovine pulmonary artery endothelial cells (BPAEC). Oxidant signaling, measured using 2Ј7Ј-dichlorofluorescin (DCFH), increased 152 Ϯ 16% during 1.5 h of cyclic strain relative to unstrained controls. The mitochondrial inhibitors diphenylene iodonium (5 M) or rotenone (2 M) attenuated this increase, whereas L-nitroarginine (100 M), allopurinol (100 M), or apocynin (30 M) had no effect. The antioxidants ebselen (5 M) and dithiodidiethyldithiocarbamate (1 mM) inhibited the strain-induced increase in oxidant signaling, but Hb (5 M) had no effect. These results indicate that strain induces oxidant release from mitochondria. Treatment with cytochalasin D (5 M) abrogated strain-induced DCFH oxidation in BPAEC, indicating that actin filaments were required for stretchinduced mitochondrial ROS generation. Cyclic strain increased FAK phosphorylation at Tyr397, but this was abolished by mitochondrial inhibitors as well as by antioxidants. Strain-induced FAK phosphorylation was abrogated by inhibition of protein kinase C (PKC) with Ro-31-8220 or Gö-6976. These findings indicate that mitochondrial oxidants generated in response to endothelial strain trigger FAK phosphorylation through a signaling pathway that involves PKC.reactive oxygen species; superoxide; cytoskeleton; cyclic stretch; protein kinase C ENDOTHELIAL DYSFUNCTION CONTRIBUTES to the pathogenesis in a wide range of diseases (9,20). In the lung, mechanical strain and shear stress represent normal stimuli to endothelial cells. However, excessive strain encountered during mechanical ventilation with large tidal volumes exacerbates lung injury and inflammation in patients with acute respiratory failure (7). An improved understanding of the mechanisms by which mechanical strain affects endothelial cell function could help to clarify how excessive lung strain exacerbates preexisting lung injury.Mechanical stretch has been shown to increase reactive oxygen species (ROS) production in endothelial cells, leading to the upregulation of cell adhesion molecules and chemokines (13, 51). Recent studies have implicated mitochondria as a source of ROS responsible for mediating flow-induced dilation in coronary arteries (32) and intercellular communication in vascular smooth muscle cells sub...

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“…Application of cyclic mechanical load at 20% strain and frequency of 1 Hz up to 48 h enhanced procollagen mRNA levels and procollagen synthesis in the presence of TGF-β1 in human dermal fibroblasts (Parsons et al, 1999). Procollagen mRNA levels were increased by 2-fold in stretched cells compared to unstretched cells with enhancement of procollagen C-proteinase (PCP) levels.…”

Section: Regulation Of Gene Expression In Fibroblasts By Mechanical Lmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

227

187

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Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

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Mechanical Load Enhances Procollagen Processing in Dermal Fibroblasts by Regulating Levels of Procollagen C-Proteinase

Cited by 80 publications

References 33 publications

Reaction of the Skin Fibroblast Cytoskeleton to Micromanipulation Interventions

Reaction of the Skin Fibroblast Cytoskeleton to Micromanipulation Interventions

Stretch-induced phosphorylation of focal adhesion kinase in endothelial cells: role of mitochondrial oxidants

Mechanoregulation of gene expression in fibroblasts

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