Role of the extracellular matrix in morphogenesis
ABSTRACT The extracellular matrix is a complex, dynamic and critical component of all tissues. It functions as a scaffold for tissue morphogenesis, provides cues for cell proliferation and differentiation, promotes the maintenance of differentiated tissues and enhances the repair response after injury. Various amounts and types of collagens, adhesion molecules, proteoglycans, growth factors and cytokines or chemokines are present in the tissue- and temporal-specific extracellular matrices. Tissue morphogenesis is mediated by multiple extracellular matrix components and by multiple active sites on some of these components. Biologically active extracellular matrix components may have use in tissue repair, regeneration and engineering, and in programming stem cells for tissue replacement.
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- "Many of these annotations, however, are not based on direct experimental observations or have not been comprehensively tested in vivo. Developmental signaling pathways active in tissue repair, such as the TGF-b, Wnt, Shh, or Bmp pathways, which emanate from secreted morphogens and are regulated by interacting ECM components (Kleinman et al, 2003), are often deregulated in chronic lung diseases, potentially causing persistent pulmonary fibrosis (Fernandez & Eickelberg, 2012). Bleomycin-induced lung injury, which induces robust fibrogenesis 2 weeks after injury, is the most frequently used animal model of pulmonary fibrosis (Mouratis & Aidinis, 2011; Bauer et al, 2015). "
ABSTRACT: The extracellular matrix (ECM) is a key regulator of tissue morpho-genesis and repair. However, its composition and architecture are not well characterized. Here, we monitor remodeling of the extra-cellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Mass spectrometry quantified 8,366 proteins from total tissue and bronchoalveolar lavage fluid (BALF) over the course of 8 weeks, surveying tissue composition from the onset of inflammation and fibrosis to its full recovery. Combined analysis of proteome, secretome, and transcriptome highlighted post-transcriptional events during tissue fibrogenesis and defined the composition of airway epithelial lining fluid. To comprehensively characterize the ECM, we developed a quantitative detergent solu-bility profiling (QDSP) method, which identified Emilin-2 and colla-gen-XXVIII as novel constituents of the provisional repair matrix. QDSP revealed which secreted proteins interact with the ECM, and showed drastically altered association of morphogens to the insoluble matrix upon injury. Thus, our proteomic systems biology study assigns proteins to tissue compartments and uncovers their dynamic regulation upon lung injury and repair, potentially contributing to the development of anti-fibrotic strategies.Molecular Systems Biology 07/2015; 11(7). DOI:10.15252/msb.20156123 · 10.87 Impact Factor
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- "Specific cell–substrate or cell to cell interactions involve components of the extracellular matrix and cell adhesion molecules as integrins, cadherins, and selectins (Bowells Sthepanie et al., 2010; Juliano, 2002; Kleinmann et al., 2003). Otherwise, unspecific adhesion mechanisms are rather resulting of the interaction due to the physico-chemical properties of the substrate such as surface hydrophobicity, surface charge, and surface functional groups (Lee et al., 2005). "
ABSTRACT: Cell mechanics provides insights in cell responses to external stress, which is an important parameter known to influence a variety of cell functions. Understanding the interdependence between mechanical stimulus, cell shape and function is essential in controlling cell culture microenvironment. In this paper, we report on the effect of cationic and anionic interfaces on cell shape and nanoparticle uptake activity of hepatocellular carcinoma cells HepG2. The shape of HepG2 cells changed from a round-like shape to a spread-like form exhibiting lamellar protrusions by incubating them on coated polystyrene well plates with polystyrene sulfonate and poly-ethylene imine (PEI), respectively. This change in shape of HepG2 cells did not influence the uptake of 49-nm particles (which entered the cells by diffusion). However, the internalization of 240-nm diameter particles was larger on cells seeded on cationic PEI. Particle uptake was measured at 4°C and 37°C; the optimal incubation time was 6 h. Cell shape and particle uptake were monitored by fluorescence and confocal microscopy. Quantification of particle internalization was carried out with flow cytometry. Microsc. Res. Tech., 2014. © 2014 Wiley Periodicals, Inc.Microscopy Research and Technique 08/2014; 77(8). DOI:10.1002/jemt.22374 · 1.15 Impact Factor
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- "Extracellular matrices (ECM) are intricate networks of collagens, glycoproteins, and proteoglycans that maintain tissue cohesion, provide physical support to tissues and organs, and determine the mechanical properties of tissues (Hynes, 2009). In addition to these structural functions, ligation of ECM proteins by various cell surface receptors can initiate biochemical signaling pathways that control cell behaviors important for tissue formation and function (Kleinman et al., 2003). In order to maintain tissue homeostasis, yet allow for changes in tissue function, ECM proteins must shift between these two functional states. "
ABSTRACT: Extracellular matrix fibronectin fibrils serve as passive structural supports for the organization of cells into tissues, yet can also actively stimulate a variety of cell and tissue functions, including cell proliferation. Factors that control and coordinate the functional activities of fibronectin fibrils are not known. Here, we compared effects of cell adhesion to vitronectin versus type I collagen on the assembly of and response to, extracellular matrix fibronectin fibrils. The amount of insoluble fibronectin matrix fibrils assembled by fibronectin-null mouse embryonic fibroblasts adherent to collagen- or vitronectin-coated substrates was not significantly different 20 h after fibronectin addition. However, the fibronectin matrix produced by vitronectin-adherent cells was ~ 10-fold less effective at enhancing cell proliferation than that of collagen-adherent cells. Increasing insoluble fibronectin levels with the fibronectin fragment, anastellin did not increase cell proliferation. Rather, native fibronectin fibrils polymerized by collagen- and vitronectin-adherent cells exhibited conformational differences in the growth-promoting, III-1 region of fibronectin, with collagen-adherent cells producing fibronectin fibrils in a more extended conformation. Fibronectin matrix assembly on either substrate was mediated by α5β1 integrins. However, on vitronectin-adherent cells, α5β1 integrins functioned in a lower activation state, characterized by reduced 9EG7 binding and decreased talin association. The inhibitory effect of vitronectin on fibronectin-mediated cell proliferation was localized to the cell-binding domain, but was not a general property of αvβ3 integrin-binding substrates. These data suggest that adhesion to vitronectin allows for the uncoupling of fibronectin fibril formation from downstream signaling events by reducing α5β1 integrin activation and fibronectin fibril extension.Matrix biology: journal of the International Society for Matrix Biology 02/2014; 34:33. DOI:10.1016/j.matbio.2014.01.017 · 5.07 Impact Factor