Basic Components of Connective Tissues and Extracellular Matrix: Fibronectin, Fibrinogen, Laminin, Elastin, Fibrillins, Fibulins, Matrilins, Tenascins and Thrombospondins

The hydraulic conductivity of a connective tissue is determined both by the fine ultrastructure of the extracellular matrix and the effects of larger particles in the interstitial space. In this study, we explored this relationship by examining the effects of 30- or 90-nm-diameter latex nanospheres or low-density lipoproteins (LDL) on the hydraulic conductivity of Matrigel, a basement membrane matrix. The hydraulic conductivity of Matrigel with latex nanospheres or LDL particles added at 4.8% weight fraction was measured and compared with the hydraulic conductivity of Matrigel alone. The LDL-derived lipids in the gel were visualized by transmission electron microscopy and were seen to have aggregated into particles up to 500 nm in size. The addition of these materials to the medium markedly decreased its hydraulic conductivity, with the LDL-derived lipids having a much larger effect than did the latex nanospheres. Debye-Brinkman theory was used to predict the effect of addition of particles to the hydraulic conductivity of the medium. The theoretical predictions matched well with the results from adding latex nanospheres to the medium. However, LDL decreased hydraulic conductivity much more than was predicted by the theory. The validation of the theoretical model for rigid particles embedded in extracellular matrix suggests that it could be used to make predictions about the influence of particulates (e.g., collagen, elastin, cells) on the hydraulic conductivity of the fine filamentous matrix (the proteoglycans) in connective tissues. In addition, the larger-than-predicted effects of lipidlike particles on hydraulic conductivity may magnify the pathology associated with lipid accumulation, such as in Bruch's membrane of the retina during macular degeneration and the blood vessel wall in atherosclerosis.

Download Full-text

LTBP1 promotes fibrillin incorporation into the extracellular matrix

10.1101/2021.12.16.473056 ◽

2021 ◽

Author(s):

Matthias Przyklenk ◽

Veronika Georgieva ◽

Fabian Metzen ◽

Sebastian Mostert ◽

Birgit Kobbe ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Wide Spectrum ◽

Extracellular Matrix Protein ◽

Connective Tissues ◽

Pathogenic Variants ◽

Human Pathology ◽

Fibrillin 1

LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillin-microfibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and -2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.

Download Full-text

Cell Mechanics Drives Migration Modes

Biophysical Reviews and Letters ◽

10.1142/s1793048020300017 ◽

2020 ◽

Vol 15 (01) ◽

pp. 1-34 ◽

Cited By ~ 1

Author(s):

Claudia Tanja Mierke

Keyword(s):

Extracellular Matrix ◽

Cell Mechanics ◽

Single Cells ◽

Biochemical Properties ◽

Migration And Invasion ◽

Environmental Cues ◽

Connective Tissues ◽

Migration Of Cells

The classical migration modes, such as mesenchymal or amoeboid migration modes, are essentially determined by molecular, morphological or biochemical properties of the cells. These specific properties facilitate the cell migration and invasion through artificial extracellular matrices mimicking the environmental conditions of connective tissues. However, during the migration of cells through narrow extracellular matrix constrictions, the specific extracellular matrix environments can either support or impair the invasion of cells. Beyond the classical molecular or biochemical properties, the migration and invasion of cells depends on intracellular cell mechanical characteristics and extracellular matrix mechanical features. The switch between cell states, such as epithelial, mesenchymal or amoeboid states, seems to be mainly based on epigenetic changes and environmental cues that induce the reversible transition of cells toward another state and thereby promote a specific migration mode. However, the exact number of migration modes is not yet clear. Moreover, it is also unclear whether every individual cell, independent of the type, can undergo a transition between all different migration modes in general. A newer theory states that the transition from the jamming to unjamming phase of clustered cells enables cells to migrate as single cells through extracellular matrix confinements. This review will highlight the mechanical features of cells and their matrix environment that regulate and subsequently determine individual migration modes. It is discussed whether each migration mode in each cell type is detectable or whether some migration modes are limited to artificially engineered matrices in vitro and can therefore not or only rarely be detected in vivo. It is specifically pointed out how the intracellular architecture and its contribution to cellular stiffness or contractility favors the employment of a distinct migration mode. Finally, this review envisions a connection between mechanical properties of cells and matrices and the choice of a distinct migration mode in confined 3D microenvironments.

Download Full-text

Hemicentin-1 is an essential extracellular matrix component of the dermal–epidermal and myotendinous junctions

Scientific Reports ◽

10.1038/s41598-021-96824-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daniela Welcker ◽

Cornelia Stein ◽

Natalia Martins Feitosa ◽

Joy Armistead ◽

Jin-Li Zhang ◽

...

Keyword(s):

Extracellular Matrix ◽

Developmental Stages ◽

Cell Types ◽

Connective Tissues ◽

Functional Behavior ◽

Transmission Electron ◽

Cellular Microenvironments ◽

And Function ◽

Myotendinous Junctions

AbstractThe extracellular matrix architecture is composed of supramolecular fibrillar networks that define tissue specific cellular microenvironments. Hemicentins (Hmcn1 and Hmcn2) are ancient and very large members (> 600 kDa) of the fibulin family, whose short members are known to guide proper morphology and functional behavior of specialized cell types predominantly in elastic tissues. However, the tissue distribution and function of Hemicentins within the cellular microenvironment of connective tissues has remained largely unknown. Performing in situ hybridization and immunofluorescence analyses, we found that mouse Hmcn1 and Hmcn2 show a complementary distribution throughout different tissues and developmental stages. In postnatal dermal–epidermal junctions (DEJ) and myotendinous junctions (MTJ), Hmcn1 is primarily produced by mesenchymal cells (fibroblasts, tenocytes), Hmcn2 by cells of epithelial origin (keratinocytes, myocytes). Hmcn1−/− mice are viable and show no overt phenotypes in tissue tensile strength and locomotion tests. However, transmission electron microscopy revealed ultrastructural basement membrane (BM) alterations at the DEJ and MTJ of Hmcn1−/− mice, pointing to a thus far unknown role of Hmcn1 for BM and connective tissue boundary integrity.

Download Full-text

Stages of Infection during the Tripartite Interaction between Xenorhabdus nematophila, Its Nematode Vector, and Insect Hosts

Applied and Environmental Microbiology ◽

10.1128/aem.70.11.6473-6480.2004 ◽

2004 ◽

Vol 70 (11) ◽

pp. 6473-6480 ◽

Cited By ~ 88

Author(s):

Mathieu Sicard ◽

Karine Brugirard-Ricaud ◽

Sylvie PagÃ¯Â¿Â½s ◽

Anne Lanois ◽

Noel E. Boemare ◽

...

Keyword(s):

Extracellular Matrix ◽

Spodoptera Littoralis ◽

Fluorescent Protein ◽

Bacterial Colonization ◽

Infective Juvenile ◽

Bacterial Cells ◽

Xenorhabdus Nematophila ◽

Insect Larvae ◽

Connective Tissues ◽

Anterior Midgut

ABSTRACT Bacteria of the genus Xenorhabdus are mutually associated with entomopathogenic nematodes of the genus Steinernema and are pathogenic to a broad spectrum of insects. The nematodes act as vectors, transmitting the bacteria to insect larvae, which die within a few days of infection. We characterized the early stages of bacterial infection in the insects by constructing a constitutive green fluorescent protein (GFP)-labeled Xenorhabdus nematophila strain. We injected the GFP-labeled bacteria into insects and monitored infection. We found that the bacteria had an extracellular life cycle in the hemolymph and rapidly colonized the anterior midgut region in Spodoptera littoralis larvae. Electron microscopy showed that the bacteria occupied the extracellular matrix of connective tissues within the muscle layers of the Spodoptera midgut. We confirmed the existence of such a specific infection site in the natural route of infection by infesting Spodoptera littoralis larvae with nematodes harboring GFP-labeled Xenorhabdus. When the infective juvenile (IJ) nematodes reached the insect gut, the bacterial cells were rapidly released from the intestinal vesicle into the nematode intestine. Xenorhabdus began to escape from the anus of the nematodes when IJs were wedged in the insect intestinal wall toward the insect hemolymph. Following their release into the insect hemocoel, GFP-labeled bacteria were found only in the anterior midgut region and hemolymph of Spodoptera larvae. Comparative infection assays conducted with another insect, Locusta migratoria, also showed early bacterial colonization of connective tissues. This work shows that the extracellular matrix acts as a particular colonization site for X. nematophila within insects.

Download Full-text

Expression of tenascin in bile duct cancer of hamster liver by combined treatment of dimethylnitrosamine with Opisthorchis viverrini infections

Journal of Helminthology ◽

10.1079/joh2002129 ◽

2002 ◽

Vol 76 (3) ◽

pp. 261-268 ◽

Cited By ~ 5

Author(s):

P. Sithithaworn ◽

K. Ando ◽

W. Limviroj ◽

S. Tesana ◽

C. Pairojkul ◽

...

Keyword(s):

Extracellular Matrix ◽

Bile Duct ◽

Golden Hamster ◽

Bile Duct Cancer ◽

Combined Treatment ◽

Opisthorchis Viverrini ◽

Essential Factor ◽

Connective Tissues ◽

Reciprocal Interactions ◽

Duct Cancer

AbstractTenascin is an extracellular matrix glycoprotein known to be an essential factor for the modulation of reciprocal interactions between the epithelium and mesenchyme during embryogenesis and tumourigenesis. The interactions between the expression of tenascin in the liver of Syrian golden hamster and the development of bile duct cancer in an Opisthorchis viverrini-associated cholangiocarcinoma model were investigated. The tenascin was expressed in connective tissues surrounding the dilated ducts, ductal rims and the stroma of cancers, and strongly in the stroma flame of necrotic cancer nodules. The mRNA signal for tenascin was also recognized in the stroma cells. The potential roles of tenascin as prognostic tumour markers are discussed.

Download Full-text

Proteomic Analysis of Human Tendon and Ligament: Solubilization and Analysis of Insoluble Extracellular Matrix in Connective Tissues

Journal of Proteome Research ◽

10.1021/acs.jproteome.6b00806 ◽

2016 ◽

Vol 15 (12) ◽

pp. 4709-4721 ◽

Cited By ~ 13

Author(s):

Nori Sato ◽

Takako Taniguchi ◽

Yuichiro Goda ◽

Hirofumi Kosaka ◽

Kosaku Higashino ◽

...

Keyword(s):

Extracellular Matrix ◽

Proteomic Analysis ◽

Connective Tissues ◽

Human Tendon

Download Full-text

Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood.

Journal of Experimental Medicine ◽

10.1084/jem.184.3.1061 ◽

1996 ◽

Vol 184 (3) ◽

pp. 1061-1073 ◽

Cited By ~ 58

Author(s):

N Ghildyal ◽

D S Friend ◽

R L Stevens ◽

K F Austen ◽

C Huang ◽

...

Keyword(s):

Extracellular Matrix ◽

Mast Cell ◽

Mast Cells ◽

Chromosome 17 ◽

Macromolecular Complex ◽

Connective Tissues ◽

Systemic Anaphylaxis ◽

Rich Domain ◽

Passive Systemic Anaphylaxis ◽

Mouse Mast Cell

The mouse mast cell protease granule tryptases designated mMCP-6 and mMCP-7 are encoded by highly homologous genes that reside on chromosome 17. Because these proteases are released when mast cells are activated, we sought a basis for distinctive functions by examining their fates in mice undergoing passive systemic anaphylaxis. 10 min-1 h after antigen (Ag) was administered to immunoglobulin (Ig)E-sensitized mice, numerous protease/proteoglycan macromolecular complexes appeared in the extracellular matrix adjacent to most tongue and heart mast cells of normal BALB/c mice and most spleen and liver mast cells of V3 mastocytosis mice. These complexes could be intensively stained by anti-mMCP-6 Ig but not by anti-mMCP-7 Ig. Shortly after Ag challenge of V3 mastocytosis mice, large amounts of properly folded, enzymatically active mMCP-7 were detected in the plasma. This plasma-localized tryptase was approximately 150 kD in its multimeric state and approximately 32 kD in its monomeric state, possessed an NH2 terminus identical to that of mature mMCP-7, and was not covalently bound to any protease inhibitor. Comparative protein modeling and electrostatic calculations disclosed that mMCP-6 contains a prominent Lys/Arg-rich domain on its surface, distant from the active site. The absence of this domain in mMCP-7 provides an explanation for its selective dissociation from the exocytosed macromolecular complex. The retention of exocytosed mMCP-6 in the extracellular matrix around activated tissue mast cells suggests a local action. In contrast, the rapid dissipation of mMCP-7 from granule cores and its inability to be inactivated by circulating protease inhibitors suggests that this tryptase cleaves proteins located at more distal sites.

Download Full-text

Selective association of an endogenous lectin with connective tissues

Journal of Cell Science ◽

10.1242/jcs.73.1.347 ◽

1985 ◽

Vol 73 (1) ◽

pp. 347-359

Author(s):

J.W. Catt ◽

F.L. Harrison

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Heart Tissue ◽

Hair Follicles ◽

Connective Tissues ◽

Alveolar Cells ◽

Tissue Sections ◽

Liver And Kidney ◽

Endogenous Lectins ◽

Or Organization

Using indirect immunofluorescence we have localized an endogenous beta-galactoside-specific lectin in resin-embedded rabbit tissue sections. The pattern of lectin distribution correlates well with biochemical estimations of lectin levels, being abundant in intestine, lung and heart tissue and relatively less abundant in skeletal muscle, liver and kidney. In all tissues lectin is found in connective tissue associated with fibroblasts and the extracellular matrix, and at the periphery of morphologically recognizable smooth muscle cells. The lectin is abundant in skin, intestine and blood vessels, where connective tissue forms the tissue architecture. It is also abundant in heart, where it is particularly associated with the capillaries and lung, where it is also found in alveolar cells. Discrete localization of lectin occurs in areas of connective tissue where epithelial elements are differentiating, such as the crypts of Lieberkuhns in the small intestine and hair follicles in the skin. From these observations we suggest that in cells of mesenchymal origin these endogenous lectins may play a role in the elaboration or organization of the extracellular matrix that regulates tissue differentiation in a number of embryonic and adult tissues.

Download Full-text

The role of matrix metalloproteinases in glaucoma pathogenesis

Ophthalmology journal ◽

10.17816/ov2015328-43 ◽

2015 ◽

Vol 8 (3) ◽

pp. 28-43 ◽

Cited By ~ 2

Author(s):

Inessa Stanislavovna Beletskaya ◽

Sergey Yurievich Astakhov

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinases ◽

Clinical Investigation ◽

Experimental Studies ◽

Glaucomatous Optic Neuropathy ◽

Connective Tissues ◽

Activity Impairment ◽

Extracellular Matrix Components ◽

The Impact

Matrix metalloproteinases belong to an enzyme family, which assure a proteolysis of practically all components of the extracellular matrix of connective tissues in normal and pathological conditions. At physiological conditions, there are evidences on the impact of this enzyme group in the embryogenesis, morphogenesis, angiogenesis, and tissue involution. The activity impairment of matrix metalloproteinases and of their specific inhibitors leads to the biosynthesis misbalance and to the degradation of extracellular matrix components; it plays a role in the development of such diseases as diabetes mellitus, rheumatoid arthritis, and arteriosclerosis. Laboratory tests and clinical investigation results confirm the role of these enzymes in tissue remodeling of different eyeball structures in glaucoma (in particular, of the trabecular meshwork and the optic disc); it leads to intraocular fluid outflow impairment and to the glaucomatous optic neuropathy development. In the review, the analysis of clinical and experimental studies is performed that are dedicated to the investigation of matrix metalloproteinases role in the pathogenesis of different glaucoma types, of the possibility to use them as biomarkers, as well as therapeutic action targets in this disease.

Download Full-text