Regulation of myofibroblast activities: Calcium pulls some strings behind the scene

Castella, Lysianne Follonier; Gabbiani, Giulio; McCulloch, Christopher A.; Hinz, Boris

doi:10.1016/j.yexcr.2010.04.033

Cited by 110 publications

(78 citation statements)

References 156 publications

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“…Myofibroblasts acquire contractile activity that is similar -but not identical -to that of smooth muscle cells (12,13). Enhanced contractility of myofibroblasts is an important phenotypic characteristic of myofibroblast differentiation (5,14,15).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis

et al. 2013

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Matrix stiffening and myofibroblast resistance to apoptosis are cardinal features of chronic fibrotic diseases involving diverse organ systems. The interactions between altered tissue biomechanics and cellular signaling that sustain progressive fibrosis are not well defined. In this study, we used ex vivo and in vivo approaches to define a mechanotransduction pathway involving Rho/Rho kinase (Rho/ROCK), actin cytoskeletal remodeling, and a mechanosensitive transcription factor, megakaryoblastic leukemia 1 (MKL1), that coordinately regulate myofibroblast differentiation and survival. Both in an experimental mouse model of lung fibrosis and in human subjects with idiopathic pulmonary fibrosis (IPF), we observed activation of the Rho/ROCK pathway, enhanced actin cytoskeletal polymerization, and MKL1 cytoplasmic-nuclear shuttling. Pharmacologic disruption of this mechanotransduction pathway with the ROCK inhibitor fasudil induced myofibroblast apoptosis through a mechanism involving downregulation of BCL-2 and activation of the intrinsic mitochondrial apoptotic pathway. Treatment with fasudil during the postinflammatory fibrotic phase of lung injury or genetic ablation of Mkl1 protected mice from experimental lung fibrosis. These studies indicate that targeting mechanosensitive signaling in myofibroblasts to trigger the intrinsic apoptosis pathway may be an effective approach for treatment of fibrotic disorders.

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Section: Introductionmentioning

confidence: 99%

Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis

et al. 2013

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“…The manner of inheritability seems to be heterogenic, most frequently it is dominating autosomal with a variable penetration, whilst more rarely it can be recessive autosomal or mitochondrial. Genetic studies showed some relationship between DD and chromosomes [6,[8][9][10]. The aberrations of the genes participating in the Wnt/beta-catenin signalling pathway seem to play a key role in the pathogenesis of the disease [11].…”

Section: Introductionmentioning

confidence: 99%

“…The occurrence of contractures is related to the disorders of the connective tissue function. Both cells and biochemical substances, such as growth factors and the substances involved in the cellular signalling pathways, take part in this process [10,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An effectiveness evaluation of the palmar fascia irradiation of patients suffering from Dupuytren’s disease

Latusek

Miszczyk²,

Gierlach³

et al. 2017

Nowotwory. Journal of Oncology

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“…Intracellular, traction forces are generated by actin-myosin contraction, which is promoted by phosphorylation of myosin light chain (MLC). In myofibroblasts, this actin-myosin contraction is mediated by the Rho A and Rho-associated kinase (ROCK) pathway, which blocks MLC phosphatase and directly phosphorylates MLC (Yee et al 2001;Nobe et al 2010;Dallon and Ehrlich 2010;Follonier Castella et al 2010). Traction forces can be blocked by the disruption of actin fibers or inhibition of the ROCK pathway, and increased by enhancement of the serum concentration in the culture medium (Grouf et al 2007;Wakatsuki et al 2000;Nobe et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Passive and active contributions to generated force and retraction in heart valve tissue engineering

Vlimmeren

Driessen-Mol

Oomens

et al. 2012

Biomech Model Mechanobiol

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In tissue engineered heart valves, cell-mediated stress development during culture results in leaflet retraction at time of implantation. This tissue retraction is partly active due to traction forces exerted by the cells and partly passive due to release of residual stress in the extracellular matrix and the cells. Within this study, we unraveled the passive and active contributions of cells and matrix to generated force and retraction in engineered heart valve tissues. Tissue engineered rectangular strips, fabricated from PGA/P4HB scaffolds and seeded with human myofibroblasts, were cultured for 4 weeks, after which the cellular contribution was changed at different levels. Elimination of the active cellular traction forces was achieved with Cytochalasin D and inhibition of the Rho-associated kinase pathway. Both active and passive cellular contributions were eliminated by lysation and/or decellularization of the tissue. Maximum cell activity was reached by increasing the fetal bovine serum concentration to 50%. The generated force decreased ∼20% after elimination of the active cellular component, ∼25% when the passive cellular component was removed as well and remained unaffected by increased serum concentrations. Passive retraction accounted for ∼60% of total retraction, of which ∼15% was residual stress in the matrix and ∼45% was passive cell retraction. Cell traction forces accounted for the remainder ∼40% of the retraction. Full activation of the cells increased retraction by ∼45%. These results illustrate the importance of the cells in the process of tissue retraction, not only actively retracting the tissue, but also in a passive manner to a large extent.

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Regulation of myofibroblast activities: Calcium pulls some strings behind the scene

Cited by 110 publications

References 156 publications

Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis

Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis

An effectiveness evaluation of the palmar fascia irradiation of patients suffering from Dupuytren’s disease

Passive and active contributions to generated force and retraction in heart valve tissue engineering

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