Extracellular matrix proteoglycan plays a pivotal role in sensitization by low pH of mechanosensitive currents in nociceptive sensory neurones

: Langerin is a C-type Lectin expressed at the surface of Langerhans cells, which play a pivotal role in protecting organisms against pathogen infections. To address this aim, Langerin presents at least two recognition sites, one Ca2+-dependent and another one independent, capable of recognizing a variety of carbohydrate ligands. In contrast to other lectins, Langerin recognizes sulfated glycosaminoglycans (GAGs), a family of complex and heterogeneous polysaccharides present in the cell membrane and the extracellular matrix at the interphase generated in the trimeric form of Langerin but absent in the monomeric form. The complexity of these oligosaccharides has impeded the development of well-defined monodisperse structures to study these interaction processes. However, in the last few decades, an improvement of synthetic developments to achieve the preparation of carbohydrate multivalent systems mimicking the GAGs has been described. Despite all these contributions, very few examples are reported where the GAG multivalent structures are used to evaluate the interaction with Langerin. These molecules should pave the way to explore these GAG-Langerin interactions.

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Harnessing the Topography of 3D Spongy-Like Electrospun Bundled Fibrous Scaffold via a Sharply Inclined Array Collector

Polymers ◽

10.3390/polym11091444 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1444 ◽

Cited By ~ 1

Author(s):

Sun Hee Cho ◽

Jeong In Kim ◽

Cheol Sang Kim ◽

Chan Hee Park ◽

In Gi Kim

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Three Dimensional ◽

Living System ◽

Pivotal Role ◽

Skin Tissue ◽

Target Tissue ◽

Fibrous Scaffold ◽

Electrospun Scaffolds ◽

Directional Change

To date, many researchers have studied a considerable number of three-dimensional (3D) cotton-like electrospun scaffolds for tissue engineering, including the generation of bone, cartilage, and skin tissue. Although numerous 3D electrospun fibrous matrixes have been successfully developed, additional research is needed to produce 3D patterned and sophisticated structures. The development of 3D fibrous matrixes with patterned and sophisticated structures (FM-PSS) capable of mimicking the extracellular matrix (ECM) is important for advancing tissue engineering. Because modulating nano to microscale features of the 3D fibrous scaffold to control the ambient microenvironment of target tissue cells can play a pivotal role in inducing tissue morphogenesis after transplantation in a living system. To achieve this objective, the 3D FM-PSSs were successfully generated by the electrospinning using a directional change of the sharply inclined array collector. The 3D FM-PSSs overcome the current limitations of conventional electrospun cotton-type 3D matrixes of random fibers.

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Regulation of Myocardial Extracellular Matrix Dynamic Changes in Myocardial Infarction and Postinfarct Remodeling

Current Cardiology Reviews ◽

10.2174/1573403x15666190509090832 ◽

2020 ◽

Vol 16 (1) ◽

pp. 11-24 ◽

Cited By ~ 1

Author(s):

Alexey Ushakov ◽

Vera Ivanchenko ◽

Alina Gagarina

Keyword(s):

Myocardial Infarction ◽

Extracellular Matrix ◽

Transforming Growth Factor ◽

Clinical Manifestations ◽

Pivotal Role ◽

Matrix Remodeling ◽

Matricellular Proteins ◽

Myocardial Repair ◽

Cellular Mechanisms

The article represents literature review dedicated to molecular and cellular mechanisms underlying clinical manifestations and outcomes of acute myocardial infarction. Extracellular matrix adaptive changes are described in detail as one of the most important factors contributing to healing of damaged myocardium and post-infarction cardiac remodeling. Extracellular matrix is reviewed as dynamic constantly remodeling structure that plays a pivotal role in myocardial repair. The role of matrix metalloproteinases and their tissue inhibitors in fragmentation and degradation of extracellular matrix as well as in myocardium healing is discussed. This review provides current information about fibroblasts activity, the role of growth factors, particularly transforming growth factor β and cardiotrophin-1, colony-stimulating factors, adipokines and gastrointestinal hormones, various matricellular proteins. In conclusion considering the fact that dynamic transformation of extracellular matrix after myocardial ischemic damage plays a pivotal role in myocardial infarction outcomes and prognosis, we suggest a high importance of further investigation of mechanisms underlying extracellular matrix remodeling and cell-matrix interactions in cardiovascular diseases.

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A nutrient sentinel stands guard outside the cell

Journal of Biological Chemistry ◽

10.1074/jbc.h118.006101 ◽

2018 ◽

Vol 293 (43) ◽

pp. 16951-16952 ◽

Cited By ~ 3

Author(s):

Davide Vigetti ◽

Ilaria Caon ◽

Alberto Passi

Keyword(s):

Extracellular Matrix ◽

Cell Death ◽

Cell Function ◽

Nutrient Sensing ◽

Pivotal Role ◽

Fundamental Importance ◽

Degradative Pathway ◽

Survival And Growth ◽

And Control ◽

Cellular Components

Nutrient sensing is a critical cell function that regulates survival and growth by adjusting metabolism. During nutrient shortage, autophagy enables the recycling of major cellular components to prevent cell death. Understanding the mechanisms that trigger and control autophagy is of fundamental importance, as this degradative pathway plays a pivotal role in many diseases. Gubbiotti et al. report the identification of a new player, the proteoglycan decorin, which functions as a nutrient sensor in the extracellular matrix and controls autophagy in the heart.

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Pivotal Role of Matrix Metalloproteinase 13 in Extracellular Matrix Turnover in Idiopathic Pulmonary Fibrosis

PLoS ONE ◽

10.1371/journal.pone.0073279 ◽

2013 ◽

Vol 8 (9) ◽

pp. e73279 ◽

Cited By ~ 44

Author(s):

Takwi Nkyimbeng ◽

Clemens Ruppert ◽

Takayuki Shiomi ◽

Bhola Dahal ◽

György Lang ◽

...

Keyword(s):

Extracellular Matrix ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Matrix Metalloproteinase ◽

Pivotal Role ◽

Matrix Metalloproteinase 13

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Is the Macrophage Phenotype Determinant for Fibrosis Development?

Biomedicines ◽

10.3390/biomedicines9121747 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1747

Author(s):

Lluis Lis-López ◽

Cristina Bauset ◽

Marta Seco-Cervera ◽

Jesús Cosín-Roger

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Wound Repair ◽

Pivotal Role ◽

High Plasticity ◽

Macrophage Phenotype ◽

Pathophysiological Process ◽

Fibrotic Process

Fibrosis is a pathophysiological process of wound repair that leads to the deposit of connective tissue in the extracellular matrix. This complication is mainly associated with different pathologies affecting several organs such as lung, liver, heart, kidney, and intestine. In this fibrotic process, macrophages play an important role since they can modulate fibrosis due to their high plasticity, being able to adopt different phenotypes depending on the microenvironment in which they are found. In this review, we will try to discuss whether the macrophage phenotype exerts a pivotal role in the fibrosis development in the most important fibrotic scenarios.

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Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00108.2012 ◽

2012 ◽

Vol 303 (3) ◽

pp. L169-L180 ◽

Cited By ~ 82

Author(s):

Aleksandar Marinković ◽

Justin D. Mih ◽

Jin-Ah Park ◽

Fei Liu ◽

Daniel J. Tschumperlin

Keyword(s):

Extracellular Matrix ◽

Lung Tissue ◽

Transforming Growth Factor ◽

Pivotal Role ◽

Lung Fibroblasts ◽

Normal Lung Tissue ◽

Fluorescent Label ◽

Normal Lung ◽

Tgf Β1 ◽

Traction Microscopy

Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation.

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The Roles of Two Distinct Regions of PINCH-1 in the Regulation of Cell Attachment and Spreading

Molecular Biology of the Cell ◽

10.1091/mbc.e10-05-0459 ◽

2010 ◽

Vol 21 (23) ◽

pp. 4120-4129 ◽

Cited By ~ 13

Author(s):

Satoko Ito ◽

Yuko Takahara ◽

Toshinori Hyodo ◽

Hitoki Hasegawa ◽

Eri Asano ◽

...

Keyword(s):

Extracellular Matrix ◽

Focal Adhesion ◽

Cell Attachment ◽

Adaptor Protein ◽

Cell Spreading ◽

Terminal Region ◽

The Other ◽

Pivotal Role ◽

Lim Domains ◽

Integrin Linked Kinase

Cells attach to the extracellular matrix (ECM) through integrins to form focal adhesion complexes, and this process is followed by the extension of lamellipodia to enable cell spreading. PINCH-1, an adaptor protein essential for the regulation of cell–ECM adhesion, consists of five tandem LIM domains and a small C-terminal region. PINCH-1 is known to interact with integrin-linked kinase (ILK) and Ras suppressor protein 1 (Rsu-1); however, the precise mechanism by which this complex regulates cell–ECM adhesion is not fully understood. We report here that the LIM1 domain of PINCH-1, which associates with ILK to stabilize the expression of this protein, is sufficient for cell attachment but not for cell spreading. In contrast, the C-terminal region of PINCH-1, which binds to Rsu-1, plays a pivotal role in cell spreading but not in cell attachment. We also show that PINCH-1 associates with Rsu-1 to activate Rac1 and that Rac1 activation is necessary for cell spreading. Thus, these data reveal how specific domains of PINCH-1 direct two independent pathways: one utilizing ILK to allow cell attachment, and the other recruiting Rsu-1 to activate Rac1 in order to promote cell spreading.

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A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase

Science Advances ◽

10.1126/sciadv.abc1404 ◽

2020 ◽

Vol 6 (48) ◽

pp. eabc1404

Author(s):

Kazuo Noda ◽

Kaori Kitagawa ◽

Takao Miki ◽

Masahito Horiguchi ◽

Tomoya O. Akama ◽

...

Keyword(s):

Extracellular Matrix ◽

Lysyl Oxidase ◽

Copper Ion ◽

Pivotal Role ◽

Cross Linking ◽

Matricellular Protein ◽

Ion Transfer ◽

Wild Type ◽

Copper Transporter ◽

Golgi Network

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (Fbln4−/−) have disrupted collagen and elastin fibers and die shortly after birth from aortic and diaphragmatic rupture. The function of fibulin-4 in ECM assembly, however, remains elusive. Here, we show that fibulin-4 is required for the activity of lysyl oxidase (LOX), a copper-containing enzyme that catalyzes the covalent cross-linking of elastin and collagen. LOX produced by Fbln4−/− cells had lower activity than LOX produced by wild-type cells due to the absence of lysine tyrosyl quinone (LTQ), a unique cofactor required for LOX activity. Our studies showed that fibulin-4 is required for copper ion transfer from the copper transporter ATP7A to LOX in the trans-Golgi network (TGN), which is a necessary step for LTQ formation. These results uncover a pivotal role for fibulin-4 in the activation of LOX and, hence, in ECM assembly.

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(Pro)collagenase (matrix metalloproteinase-1) is present in rodent osteoclasts and in the underlying bone-resorbing compartment

Journal of Cell Science ◽

10.1242/jcs.106.4.1071 ◽

1993 ◽

Vol 106 (4) ◽

pp. 1071-1082 ◽

Cited By ~ 6

Author(s):

J.M. Delaisse ◽

Y. Eeckhout ◽

L. Neff ◽

C. Francois-Gillet ◽

P. Henriet ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinase ◽

Low Ph ◽

Cysteine Proteinases ◽

Bone Surface ◽

Matrix Metalloproteinase 1 ◽

The Matrix ◽

Lines Of Evidence

Osteoclasts resorb the extracellular matrix of bone by secreting enzymes and acid into a sealed-off compartment that they form upon attachment to the bone surface. Although the lysosomal cysteine proteinases can degrade collagen after the demineralization of bone at low pH, several lines of evidence suggest that collagenase (matrix metalloproteinase-1, EC 3.4.24.7) may also be involved in this process. The question of whether collagenase is present in the osteoclast and/or in the bone-resorbing compartment has however not been resolved. We have prepared an anti-mouse collagenase antiserum and affinity-purified an IgG fraction that specifically immunoblots and immunoprecipitates (pro)collagenase. Using these antibodies, we demonstrate by immunolocalization the presence of (pro)collagenase both in the osteoclasts and in the extracellular subosteoclastic bone-resorbing compartment. These specific localizations were observed not only in mice but also in rat and rabbit osteoclasts and using not only the antibody we have prepared but also antibodies raised in other laboratories against rat (Jeffrey et al., J. Cell. Physiol. 143, 396–403, 1990) and rabbit (Brinckerhoff et al., J. Biol. Chem. 265, 22262–22269, 1990) collagenase. Intracellular collagenase was observed in the osteoclasts whether the cells were plated on bone or cultured on glass coverslips. It is proposed that osteoclastic collagenase is secreted in the resorbing compartment where it may cooperate with the lysosomal cysteine proteinases in the degradation of the collagen component of the matrix during the resorption of bone.

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