Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling

Mechanical forces between cells and extracellular matrix (ECM) influence cell shape and function. Tendons are ECM-rich tissues connecting muscles with bones that bear extreme tensional force. Analysis of transgenic zebrafish expressing mCherry driven by the tendon determinant scleraxis reveals that tendon fibroblasts (tenocytes) extend arrays of microtubule-rich projections at the onset of muscle contraction. In the trunk, these form a dense curtain along the myotendinous junctions at somite boundaries, perpendicular to myofibers, suggesting a role as force sensors to control ECM production and tendon strength. Paralysis or destabilization of microtubules reduces projection length and surrounding ECM, both of which are rescued by muscle stimulation. Paralysis also reduces SMAD3 phosphorylation in tenocytes and chemical inhibition of TGFβ signaling shortens tenocyte projections. These results suggest that TGFβ, released in response to force, acts on tenocytes to alter their morphology and ECM production, revealing a feedback mechanism by which tendons adapt to tension.

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Extracellular Matrix Organization, Structure, and Function

Calcific Aortic Valve Disease ◽

10.5772/52842 ◽

2013 ◽

Cited By ~ 9

Author(s):

Dena Wiltz ◽

C. Alexander ◽

Liezl R. ◽

Alicia A. Blancas ◽

Matthew C. ◽

...

Keyword(s):

Extracellular Matrix ◽

Organization Structure ◽

Structure And Function ◽

Matrix Organization ◽

And Function

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Enhanced Structure and Function of Stem Cell-Derived Beta-Like Cells Cultured on Extracellular Matrix

SSRN Electronic Journal ◽

10.2139/ssrn.3525552 ◽

2020 ◽

Author(s):

Reena Singh ◽

Richard Tan ◽

Clara Tran ◽

Thomas Loudovaris ◽

Helen E. Thomas ◽

...

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Structure And Function ◽

And Function ◽

Cells Cultured

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Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links

Biomolecules ◽

10.3390/biom11020336 ◽

2021 ◽

Vol 11 (2) ◽

pp. 336

Author(s):

Roberta Melchionna ◽

Paola Trono ◽

Annalisa Tocci ◽

Paola Nisticò

Keyword(s):

Cancer Progression ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Tissue Homeostasis ◽

Actin Dynamics ◽

Human Tissues ◽

Cellular Functions ◽

Tgfβ Signaling ◽

Physical Mechanisms ◽

And Function

Human tissues, to maintain their architecture and function, respond to injuries by activating intricate biochemical and physical mechanisms that regulates intercellular communication crucial in maintaining tissue homeostasis. Coordination of the communication occurs through the activity of different actin cytoskeletal regulators, physically connected to extracellular matrix through integrins, generating a platform of biochemical and biomechanical signaling that is deregulated in cancer. Among the major pathways, a controller of cellular functions is the cytokine transforming growth factor β (TGFβ), which remains a complex and central signaling network still to be interpreted and explained in cancer progression. Here, we discuss the link between actin dynamics and TGFβ signaling with the aim of exploring their aberrant interaction in cancer.

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Modulation of Innate Immune Toxicity by Silver Nanoparticle Exposure and the Preventive Effects of Pterostilbene

International Journal of Molecular Sciences ◽

10.3390/ijms22052536 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2536

Author(s):

Rong-Jane Chen ◽

Chiao-Ching Huang ◽

Rosita Pranata ◽

Yu-Hsuan Lee ◽

Yu-Ying Chen ◽

...

Keyword(s):

Silver Nanoparticles ◽

Good Alternative ◽

Innate Immune ◽

Toxic Effects ◽

Transgenic Zebrafish ◽

Zebrafish Model ◽

Cytokines And Chemokines ◽

Living Organisms ◽

And Function ◽

Immune Toxicity

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.

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Peroxynitrite modifies the structure and function of the extracellular matrix proteoglycan perlecan by reaction with both the protein core and the heparan sulfate chains

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2010.04.018 ◽

2010 ◽

Vol 49 (2) ◽

pp. 282-293 ◽

Cited By ~ 30

Author(s):

Eleanor C. Kennett ◽

Martin D. Rees ◽

Ernst Malle ◽

Astrid Hammer ◽

John M. Whitelock ◽

...

Keyword(s):

Extracellular Matrix ◽

Heparan Sulfate ◽

Structure And Function ◽

Protein Core ◽

And Function

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Epidermal growth factor modifies the expression and function of extracellular matrix adhesion receptors expressed by peritoneal mesothelial cells from patients on CAPD

Nephrology Dialysis Transplantation ◽

10.1093/ndt/14.5.1208 ◽

1999 ◽

Vol 14 (5) ◽

pp. 1208-1216 ◽

Cited By ~ 37

Author(s):

D Leavesley

Keyword(s):

Extracellular Matrix ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Mesothelial Cells ◽

Adhesion Receptors ◽

Peritoneal Mesothelial Cells ◽

Matrix Adhesion ◽

Epidermal Growth ◽

And Function

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Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411010120050201 ◽

2001 ◽

Vol 12 (5) ◽

pp. 373-398 ◽

Cited By ~ 144

Author(s):

Bjorn Steffensen ◽

Lari Häkkinen ◽

Hannu Larjava

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Matrix Metalloproteinases ◽

Wound Repair ◽

Enzyme Activation ◽

Processing Enzymes ◽

The Matrix ◽

Signaling Receptors ◽

State Of Rest ◽

And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

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Regulation of human lung fibroblast phenotype and function by vitronectin and vitronectin integrins

Journal of Cell Science ◽

10.1242/jcs.114.19.3507 ◽

2001 ◽

Vol 114 (19) ◽

pp. 3507-3516 ◽

Cited By ~ 1

Author(s):

Amelia K. Scaffidi ◽

Yuben P. Moodley ◽

Markus Weichselbaum ◽

Philip J. Thompson ◽

Darryl A. Knight

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Monoclonal Antibodies ◽

Human Lung ◽

Stress Fibers ◽

Collagen Gels ◽

Human Lung Fibroblast ◽

Myofibroblast Phenotype ◽

And Function ◽

Blocking Antibodies

Myofibroblasts, characterised by high expression of α-smooth muscle actin (α-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast phenotype are unknown but are likely to involve signals from the extracellular matrix transmitted via specific integrins. Vitronectin is a glycoprotein released during inflammation and has been shown to regulate the phenotype of vascular smooth muscle cells via αv and β1 integrins. In the current study we have examined whether vitronectin influences the phenotype and function of normal human lung fibroblasts (HFL-1). Incubation of HFL-1 cells with vitronectin induced a concentration-dependent reduction in α-SMA expression. By contrast, function-blocking monoclonal antibodies to the vitronectin integrins αv, β1, αvβ3 and αvβ5 induced the expression of α-SMA and its organization into stress fibers. Expression of α-SMA induced by all function-blocking monoclonal antibodies was abrogated by inhibition of protein kinase C and phosphatidylinositol-3 kinase, but the effects of inhibition of other signalling pathways was integrin dependent. Exposure to other extracellular matrix proteins such as fibronectin, collagen or their integrins did not influence expression of α-SMA. The expression and organization of α-SMA induced by exposure to function-blocking antibodies was translated into an augmented capacity of HFL-1 cells to contract fibroblast populated collagen gels. By contrast, contraction of collagen gels following incubation with vitronectin was not significantly different to control. This study has shown that vitronectin influences the phenotype and behaviour of HFL-1 cells by downregulating the expression of α-SMA and reducing their contractile ability. By contrast, occupancy of specific integrins by function-blocking antibodies upregulated the expression of α-SMA and induced the formation of functional stress fibers capable of contracting collagen gels. These results suggest that vitronectin modulates the fibroblast-myofibroblast phenotype, implying an important role in the remodelling process during lung development or response to injury.

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