scholarly journals Syndecan-4–dependent Rac1 regulation determines directional migration in response to the extracellular matrix

2007 ◽  
Vol 177 (3) ◽  
pp. 527-538 ◽  
Author(s):  
Mark D. Bass ◽  
Kirsty A. Roach ◽  
Mark R. Morgan ◽  
Zohreh Mostafavi-Pour ◽  
Tobias Schoen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Leading Edge ◽  
Migratory Behavior ◽  
Membrane Protrusion ◽  
Wild Type ◽  
Directional Migration ◽  
Rac1 Activity ◽  
The Matrix ◽  
Protein Kinase Cα

Cell migration in wound healing and disease is critically dependent on integration with the extracellular matrix, but the receptors that couple matrix topography to migratory behavior remain obscure. Using nano-engineered fibronectin surfaces and cell-derived matrices, we identify syndecan-4 as a key signaling receptor determining directional migration. In wild-type fibroblasts, syndecan-4 mediates the matrix-induced protein kinase Cα (PKCα)–dependent activation of Rac1 and localizes Rac1 activity and membrane protrusion to the leading edge of the cell, resulting in persistent migration. In contrast, syndecan-4–null fibroblasts migrate randomly as a result of high delocalized Rac1 activity, whereas cells expressing a syndecan-4 cytodomain mutant deficient in PKCα regulation fail to localize active Rac1 to points of matrix engagement and consequently fail to recognize and respond to topographical changes in the matrix.

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

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
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.

Epithelial-derived TGF-β2 modulates basal and wound-healing subepithelial matrix homeostasis

2006 ◽  
Vol 291 (6) ◽  
pp. L1277-L1285 ◽  
Author(s):  
H. Garrett R. Thompson ◽  
Justin D. Mih ◽  
Tatiana B. Krasieva ◽  
Bruce J. Tromberg ◽  
Steven C. George
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Transforming Growth Factor ◽  
Second Harmonic ◽  
Smooth Muscle Actin ◽  
Critical Role ◽  
The Matrix

The epithelium influences the mesenchyme during dynamic processes such as embryogenesis, wound healing, fibrosis, and carcinogenesis. Since transforming growth factor-β (TGF-β) modulates these processes, we hypothesized that epithelial-derived TGF-β also plays a critical role in maintaining the extracellular matrix at basal conditions. We utilized an in vitro model of the epithelial-mesenchymal trophic unit in the human airways to determine the role of epithelial-derived TGF-β in modulating the extracellular matrix under basal and wound-healing conditions. When differentiated at an air-liquid interface, the human bronchial epithelium produces active TGF-β2 at a concentration of 50–70 pg/ml, whereas TGF-β1 is undetectable. TGF-β2 increases two- to threefold following scrape injury in a dose-dependent fashion and significantly enhances both α-smooth muscle actin expression in the underlying collagen-embedded fibroblasts and secretion of tenascin-C into the matrix. Multiphoton microscopy demonstrates substantially enhanced second harmonic generation from fibrillar collagen in the matrix. Pretreatment of the matrix with either sirolimus (2.5 nM) or paclitaxel (10 nM) abolishes the increases in both TGF-β2 and second harmonic generation in response to epithelial injury. In the absence of the epithelium, exogenous active TGF-β2 (0–400 pg/ml) produces a biphasic response in the second harmonic signal with a minimum occurring at the epithelial-derived basal level. We conclude that epithelial-derived TGF-β2 is secreted in response to injury, significantly alters the bulk optical properties of the extracellular matrix, and its tight regulation may be required for normal collagen homeostasis.

scholarly journals Amyloid fibers provide structural integrity to Bacillus subtilis biofilms

2010 ◽  
Vol 107 (5) ◽  
pp. 2230-2234 ◽  
Author(s):  
Diego Romero ◽  
Claudio Aguilar ◽  
Richard Losick ◽  
Roberto Kolter
Keyword(s):  
Extracellular Matrix ◽  
Bacillus Subtilis ◽  
Biological Activity ◽  
Biofilm Formation ◽  
Structural Integrity ◽  
Wild Type ◽  
Amyloid Fibers ◽  
The Matrix ◽  
Biochemical Analyses ◽  
Main Components

Bacillus subtilis forms biofilms whose constituent cells are held together by an extracellular matrix. Previous studies have shown that the protein TasA and an exopolysaccharide are the main components of the matrix. Given the importance of TasA in biofilm formation, we characterized the physicochemical properties of this protein. We report that purified TasA forms fibers of variable length and 10–15 nm in width. Biochemical analyses, in combination with the use of specific dyes and microscopic analyses, indicate that TasA forms amyloid fibers. Consistent with this hypothesis, TasA fibers required harsh treatments (e.g., formic acid) to be depolymerized. When added to a culture of a tasA mutant, purified TasA restored wild-type biofilm morphology, indicating that the purified protein retained biological activity. We propose that TasA forms amyloid fibers that bind cells together in the biofilm.

scholarly journals Cellular events and biomarkers of wound healing

2012 ◽  
Vol 45 (02) ◽  
pp. 220-228 ◽  
Author(s):  
Shah Jumaat Mohd. Yussof ◽  
Effat Omar ◽  
Dinker R. Pai ◽  
Suneet Sood
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Chronic Wounds ◽  
Keratinocyte Proliferation ◽  
Wound Fluid ◽  
Inflammatory Phase ◽  
Cellular Events ◽  
The Matrix ◽  
Secondary Closure

ABSTRACTResearchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

scholarly journals Active agents loaded extracellular matrix mimetic electrospun membranes for wound healing applications

2021 ◽  
pp. 102500
Author(s):  
Sumama Nuthana Kalva ◽  
Robin Augustine ◽  
Abdulla Al Mamun ◽  
Yogesh Bharat Dalvi ◽  
Namitha Vijay ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Electrospun Membranes

scholarly journals Can biomarkers of extracellular matrix remodelling and wound healing be used to identify high risk patients infected with SARS-CoV-2?: lessons learned from pulmonary fibrosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
D. J. Leeming ◽  
F. Genovese ◽  
J. M. B. Sand ◽  
D. G. K. Rasmussen ◽  
C. Christiansen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Interstitial Lung Diseases ◽  
Lessons Learned ◽  
Lung Function Decline ◽  
Tissue Remodelling

AbstractPulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor’s consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biomarkers that in patients with SARS-Cov-2 infection are able to; (1) identify patients in most need of medical care prior to admittance to an intensive care unit (ICU), and; (2) identify patients post-infection at risk of developing persistent fibrosis of lungs with subsequent impaired quality of life and increased morbidity and mortality. An intense amount of research have focused on wound healing and Extracellular Matrix (ECM) remodelling of the lungs related to lung function decline in pulmonary fibrosis (PF). A range of non-invasive serological biomarkers, reflecting tissue remodelling, and fibrosis have been shown to predict risk of acute exacerbations, lung function decline and mortality in PF and other interstitial lung diseases (Sand et al. in Respir Res 19:82, 2018). We suggest that lessons learned from such PF studies of the pathological processes leading to lung function decline could be used to better identify patients infected with SARS-Co-V2 at most risk of acute deterioration or persistent fibrotic damage of the lung and could consequently be used to guide treatment decisions.

A multifunctional substance P-conjugated chitosan hydrochloride hydrogel accelerates full-thickness wound healing by enhancing synchronized vascularization, extracellular matrix deposition, and nerve regeneration

2021 ◽  
Author(s):  
Hao Li ◽  
Mengna Li ◽  
Pei Liu ◽  
Kai-Yang Wang ◽  
Haoyu Fang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Full Thickness ◽  
Matrix Deposition ◽  
Chitosan Hydrochloride ◽  
Reconstructive Microsurgery ◽  
Extracellular Matrix Deposition ◽  
Advanced Biomaterials ◽  
Native Skin ◽  
Full Thickness Wound

Due to the native skin limitations and the complexity of reconstructive microsurgery, advanced biomaterials are urgently required to promote wound healing for severe skin defects caused by accidents and disasters....

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