Role of physical forces in compensatory growth of the lung

1989 ◽  
Vol 257 (4) ◽  
pp. L179-L189 ◽  
Author(s):  
D. E. Rannels
Keyword(s):  
Cell Shape ◽  
Compensatory Growth ◽  
Normal Lung ◽  
Physical Factors ◽  
Physical Force ◽  
Isolated Cells ◽  
Paracrine Factors ◽  
Extracellular Matrix Components ◽  
Hormonal Modulation ◽  
Physical Forces

In many species, partial resection of the lung leads to rapid compensatory growth of the remaining tissue to restore normal lung mass and function. The response to partial pneumonectomy is closely controlled; both its rate and nature are subject to hormonal modulation. Physical factors, particularly distortion of the lung by altered inflation, are likely involved in regulation of the response, although the details of the regulatory mechanisms are not understood. In a number of tissues including the lung, application of external physical force leads to both acute and long-term changes in metabolism. In some cases these include cell growth and division, along with increased production of extracellular matrix components. Similar responses have been described after application of stress to isolated cells in culture. Independent lines of investigation have defined dramatic influences of cell shape on growth, differentiation, and metabolism, but stress-strain relationships at the cellular or subcellular levels are poorly defined. The mechanisms by which changes in cell shape are transduced to intracellular signals likely depend on receptor-mediated interactions with the cytoskeleton, but strain-associated transduction pathways may involve stretch-sensitive ion channels, G protein-dependent reactions, the action of locally produced autocrine or paracrine factors, or a combination of these factors. These observations suggest a general model of the response to pneumonectomy that may be used to formulate specific hypotheses as a basis for future investigations. This approach will provide insight into the mechanisms by which physical forces influence growth and metabolism in the lung and other tissues.

Syndecan, a developmentally regulated cell surface proteoglycan that binds extracellular matrix and growth factors

1990 ◽  
Vol 327 (1239) ◽  
pp. 171-186 ◽  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Cell Surface ◽  
Cell Shape ◽  
Heparan Sulphate ◽  
Tissue Type ◽  
Cell Behaviour ◽  
Extracellular Matrix Components ◽  
Cellular Behaviour ◽  
Cell Surface Proteoglycan

Cellular behaviour during development is dictated, in part, by the insoluble extracellular matrix and the soluble growth factor peptides, the major molecules responsible for integrating cells into morphologically and functionally defined groups. These extracellular molecules influence cellular behaviour by binding at the cell surface to specific receptors that transduce intracellular signals in various ways not yet fully clear. Syndecan, a cell surface proteoglycan found predominantly on epithelia in mature tissues binds both extracellular matrix components (fibronectin, collagens I, III, V, and thrombospondin) and basic fibroblast growth factor (bFGF). Syndecan consists of chondroitin sulfate and heparan sulphate chains linked to a 31 kilodalton (kDa) integral membrane protein. Syndecan represents a family of integral membrane proteoglycans that differ in extracellular domains, but share cytoplasmic domains. Syndecan behaves as a matrix receptor: it binds selectively to components of the extracellular matrix, associates intracellularly with the actin cytoskeleton when cross-linked at the cell surface, its extracellular domain is shed upon cell rounding and it localizes solely to basolateral surfaces of simple epithelia. Mammary epithelial cells made syndecan-deficient become fibroblastic in morphology and cell behaviour, showing that syndecan maintains epithelial cell morphology. Syndecan changes in quantity, location and structure during development: it appears initially on four-cell embryos (prior to its known matrix ligands), becomes restricted in the pre-implementation embryo to the cells that will form the embryo proper, changes its expression due to epithelial-mesenchymal interactions (for example, induced in kidney mesenchyme by the ureteric bud), and with association of cells with extracellular matrix (for example, during B-cell differentiation), and ultimately, in mature tissues becomes restricted to epithelial tissues. The number and size of its glycosaminoglycan chains vary with changes in cell shape and organization yielding tissue type-specific polymorphic forms of syndecan. Its interactions with the major extracellular effector molecules that influence cell behaviour, its role in maintaining cell shape and its spatial and temporal changes in expression during development indicate that syndecan is involved in morphogenesis.

scholarly journals Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses

2015 ◽  
Vol 308 (12) ◽  
pp. H1451-H1462 ◽  
Author(s):  
Shampa Chatterjee ◽  
Keigi Fujiwara ◽  
Néstor Gustavo Pérez ◽  
Masuko Ushio-Fukai ◽  
Aron B. Fisher
Keyword(s):  
Cellular Proliferation ◽  
Signaling Cascades ◽  
Physical Force ◽  
Society Meeting ◽  
Receptor Kinases ◽  
Final Response ◽  
Pan American ◽  
Physical Forces ◽  
And Function ◽  
Cellular Components

Cells are constantly exposed to mechanical forces that play a role in modulating cellular structure and function. The cardiovascular system experiences physical forces in the form of shear stress and stretch associated with blood flow and contraction, respectively. These forces are sensed by endothelial cells and cardiomyocytes and lead to responses that control vascular and cardiac homeostasis. This was highlighted at the Pan American Physiological Society meeting at Iguassu Falls, Brazil, in a symposium titled “Mechanosignaling in the Vasculature.” This symposium presented recent research that showed the existence of a vital link between mechanosensing and downstream redox sensitive signaling cascades. This link helps to transduce and transmit the physical force into an observable physiological response. The speakers showcased how mechanosensors such as ion channels, membrane receptor kinases, adhesion molecules, and other cellular components transduce the force via redox signals (such as reactive oxygen species and nitric oxide) to receptors (transcription factors, growth factors, etc.). Receptor activated pathways then lead to cellular responses including cellular proliferation, contraction, and remodeling. These responses have major relevance to the physiology and pathophysiology of various cardiovascular diseases. Thus an understanding of the complex series of events, from the initial sensing through the final response, is essential for progress in this field. Overall, this symposium addressed some important emerging concepts in the field of mechanosignaling and the eventual pathophysiological responses.

scholarly journals The Correlation of Mental and Physical Force; or, Man a Part of Nature

1859 ◽  
Vol 6 (31) ◽  
pp. 50-78 ◽  
Author(s):  
Henry Maudsley
Keyword(s):  
List Type ◽  
Type Number ◽  
Unity Of Science ◽  
Physical Force ◽  
Physical Forces ◽  
Mutual Relations

1“Man and his Dwelling Place.” London: J. W. Parker & Sons, West Strand.2“Essay on the Unity of Science,” by Rev. B. Powell, F.K.S., &c.3“Order of Nature,” by the Rev. B. Powell.4Grove, on “The Correlation of the Physical Forces.”5On “The Mutual Relations of the Vital and Physical Forces.” Dr. Carpenter, Philosoph. Transac., 1850.6Oersted's “Soul in Nature.”

Growth and biomechanics of shoot organs

2019 ◽  
Vol 70 (14) ◽  
pp. 3573-3585 ◽  
Author(s):  
Emilie Echevin ◽  
Constance Le Gloanec ◽  
Nikolina Skowrońska ◽  
Anne-Lise Routier-Kierzkowska ◽  
Agata Burian ◽  
...  
Keyword(s):  
Physical Factors ◽  
Multidisciplinary Research ◽  
Plant Organs ◽  
Complex Interactions ◽  
Lateral Organs ◽  
Control Growth ◽  
Tremendous Progress ◽  
Mechanical Basis ◽  
Physical Forces

AbstractPlant organs arise through complex interactions between biological and physical factors that control morphogenesis. While there has been tremendous progress in the understanding of the genetics behind development, we know much less about how mechanical forces control growth in plants. In recent years, new multidisciplinary research combining genetics, live-imaging, physics, and computational modeling has begun to fill this gap by revealing the crucial role of biomechanics in the establishment of plant organs. In this review, we provide an overview of our current understanding of growth during initiation, patterning, and expansion of shoot lateral organs. We discuss how growth is controlled by physical forces, and how mechanical stresses generated during growth can control morphogenesis at the level of both cells and tissues. Understanding the mechanical basis of growth and morphogenesis in plants is in its early days, and many puzzling facts are yet to be deciphered.

Gene expression profiling in lung fibroblasts reveals new players in alveolarization

2007 ◽  
Vol 32 (1) ◽  
pp. 128-141 ◽  
Author(s):  
Olivier Boucherat ◽  
Marie-Laure Franco-Montoya ◽  
Christelle Thibault ◽  
Roberto Incitti ◽  
Bernadette Chailley-Heu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Retinoic Acid Receptor ◽  
Lung Fibroblasts ◽  
Fetal Life ◽  
Isolated Cells ◽  
Signal Molecule ◽  
Expression Of Genes ◽  
Extracellular Matrix Components

Little is known about the molecular basis of lung alveolarization. We used a microarray profiling strategy to identify novel genes that may regulate the secondary septation process. Rat lung fibroblasts were extemporaneously isolated on postnatal days 2, 7, and 21, i.e., before, during, and after septation, respectively. Total RNA was extracted, and cRNAs were hybridized to Affymetrix rat genome 230 2.0 microarrays. Expression levels of a selection of genes were confirmed by real-time PCR. In addition to genes already known to be upregulated during alveolarization including drebrin, midkine, Fgfr3, and Fgfr4, the study allowed us to identify two remarkable groups of genes with opposite profiles, i.e., gathering genes either transiently up- or downregulated on day 7. The former group includes the transcription factors retinoic acid receptor ( RXR)-γ and homeobox ( Hox) a2, a4, and a5 and genes involved in Wnt signaling ( Wnt5a, Fzd1, and Ndp); the latter group includes the extracellular matrix components Comp and Opn and the signal molecule Slfn4. Profiling in whole lung from fetal life to adulthood confirmed that changes were specific for alveolarization. Two treatments that arrest septation, hyperoxia and dexamethasone, inhibited the expression of genes that are upregulated during alveolarization and conversely enhanced that of genes weakly expressed during alveolarization and upregulated thereafter. The possible roles of these genes in secondary septation are discussed. Gene expression profiling analysis on freshly isolated cells represents a powerful approach to provide new information about differential regulation of genes during alveolarization and pathways potentially involved in the pathogenesis of bronchopulmonary dysplasia.

scholarly journals Evidence of proteins, chromosomes and chemical markers of DNA in exceptionally preserved dinosaur cartilage

2020 ◽  
Vol 7 (4) ◽  
pp. 815-822 ◽  
Author(s):  
Alida M Bailleul ◽  
Wenxia Zheng ◽  
John R Horner ◽  
Brian K Hall ◽  
Casey M Holliday ◽  
...  
Keyword(s):  
Collagen Type ◽  
Molecular Level ◽  
Nuclear Material ◽  
Chemical Markers ◽  
Isolated Cells ◽  
Molecular Features ◽  
In Situ Preservation ◽  
Calcified Cartilage ◽  
Extracellular Matrix Components

Abstract A histological ground-section from a duck-billed dinosaur nestling (Hypacrosaurus stebingeri) revealed microstructures morphologically consistent with nuclei and chromosomes in cells within calcified cartilage. We hypothesized that this exceptional cellular preservation extended to the molecular level and had molecular features in common with extant avian cartilage. Histochemical and immunological evidence supports in situ preservation of extracellular matrix components found in extant cartilage, including glycosaminoglycans and collagen type II. Furthermore, isolated Hypacrosaurus chondrocytes react positively with two DNA intercalating stains. Specific DNA staining is only observed inside the isolated cells, suggesting endogenous nuclear material survived fossilization. Our data support the hypothesis that calcified cartilage is preserved at the molecular level in this Mesozoic material, and suggest that remnants of once-living chondrocytes, including their DNA, may preserve for millions of years.

Cell shape and organization of cytoskeleton and surface fibronectin in non-tumorigenic and tumorigenic rat liver cultures

1982 ◽  
Vol 54 (1) ◽  
pp. 47-67
Author(s):  
G.A. Bannikov ◽  
V.I. Guelstein ◽  
R. Montesano ◽  
I.S. Tint ◽  
L. Tomatis ◽  
...  
Keyword(s):  
Rat Liver ◽  
Cell Shape ◽  
Morphological Changes ◽  
Complete Disappearance ◽  
Isolated Cells ◽  
Cell Sheets ◽  
Common Features ◽  
Microfilament Bundles ◽  
Epithelial Cultures ◽  
Cytoskeletal Elements

Morphological changes associated with neoplastic transformation of epithelial cells were studied in a series of IAR cell lines derived from rat liver. The series included three independently obtained, non-tumorigenic lines and five derived, tumorigenic lines. The morphology of cell surfaces was observed by scanning electron microscopy; the distribution of actin, tubulin and fibronectin was determined by indirect immunofluorescence. All the non-tumorigenic lines had a typical epithelioid morphology: isolated cells of these lines spread on the substratum had a discoid shape and contained circular, marginal bundles of microfilaments and microtubules. In denser areas, the cells formed monolayered sheets with characteristic marginal bundles of microfilaments near the free edges. Decreased spreading of isolated cells on the substratum was the characteristic feature that distinguished tumorigenic lines from their non-tumorigenic parent lines. In particular a decrease in the size of the ring-like, peripheral lamella and its disintegration into several discrete lamellar zones were often observed; as a result, the cell shape was altered from discoid to polygonal or elongated. The altered distribution of microfilament bundles and microtubules was characteristic in elongated cells; the pattern of the cytoskeletal elements of these cells resembled that of polarized fibroblasts. Complete disappearance of microfilament bundles was observed in cells of only one tumorigenic line. Various degrees of disorganization of monolayered cell sheets were observed in tumorigenic cultures, accompanied by an altered distribution of microfilament bundles. The alterations in the fibronectin-containing structures were more complex: there were often fewer fibronectin “spots' and fibrils at the lower surfaces of cells of tumorigenic cultures as compared with those of non-tumorigenic ones; there were more fibrils in dense cultures of certain lines but fewer in others. It is concluded that alterations in the ability to spread on the substratum and to form cell-cell contacts are common features of morphologically transformed fibroblastic and epithelial cultures. However, the actual changes in the cytoskeletal structures that accompany these alterations are different in transformed cultures of various tissue types.

scholarly journals Functional mapping of SPARC: peptides from two distinct Ca+(+)-binding sites modulate cell shape.

1990 ◽  
Vol 111 (6) ◽  
pp. 3065-3076 ◽  
Author(s):  
T F Lane ◽  
E H Sage
Keyword(s):  
Extracellular Matrix ◽  
Cell Shape ◽  
Solid Phase ◽  
Cell Spreading ◽  
Dependent Manner ◽  
Binding Assays ◽  
Extracellular Matrix Components ◽  
Multiple Regions ◽  
Matrix Components ◽  
Inhibitor Of Protein Synthesis

Using synthetic peptides, we have identified two distinct regions of the glycoprotein SPARC (Secreted Protein Acidic and Rich in Cysteine) (osteonectin/BM-40) that inhibit cell spreading. One of these sites also contributes to the affinity of SPARC for extracellular matrix components. Peptides representing subregions of SPARC were synthesized and antipeptide antibodies were produced. Immunoglobulin fractions of sera recognizing an NH2-terminal peptide (designated 1.1) blocked SPARC-mediated anti-spreading activity. Furthermore, when peptides were added to newly plated endothelial cells or fibroblasts, peptide 1.1 and a peptide corresponding to the COOH terminal EF-hand domain (designated 4.2) inhibited cell spreading in a dose-dependent manner. These peptides exhibited anti-spreading activity at concentrations from 0.1 to 1 mM. The ability of peptides 1.1 and 4.2 to modulate cell shape was augmented by an inhibitor of protein synthesis and was blocked by specific antipeptide immunoglobulins. In addition to blocking cell spreading, peptide 4.2 competed for binding of [125I]SPARC and exhibited differential affinity for extracellular matrix molecules in solid-phase binding assays. The binding of peptide 4.2 to matrix components was Ca+(+)-dependent and displayed specificities similar to those of native SPARC. These studies demonstrate that both anti-spreading activity and affinity for collagens are functions of unique regions within the SPARC amino acid sequence. The finding that two separate regions of the SPARC protein contribute to its anti-spreading activity lead us to propose that multiple regions of the protein act in concert to regulate the interactions of cells with their extracellular matrix.

scholarly journals An Inducible and Vascular Smooth Muscle Cell-Specific Pink1 Knockout Induces Mitochondrial Energetic Dysfunction during Atherogenesis

2021 ◽  
Vol 22 (18) ◽  
pp. 9993
Author(s):  
Craig K. Docherty ◽  
Jordan Bresciani ◽  
Andy Carswell ◽  
Amrita Chanderseka ◽  
Elaine Friel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Glycolytic Metabolism ◽  
Wild Type ◽  
Hexokinase Ii ◽  
Isolated Cells ◽  
Extracellular Matrix Components

DNA damage and mitochondrial dysfunction are defining characteristics of aged vascular smooth muscle cells (VSMCs) found in atherosclerosis. Pink1 kinase regulates mitochondrial homeostasis and recycles dysfunctional organelles critical for maintaining energetic homeostasis. Here, we generated a new vascular-specific Pink1 knockout and assessed its effect on VSMC-dependent atherogenesis in vivo and VSMC energetic metabolism in vitro. A smooth muscle cell-specific and MHC-Cre-inducible flox’d Pink1f/f kinase knockout was made on a ROSA26+/0 and ApoE−/− C57Blk6/J background. Mice were high fat fed for 10 weeks and vasculature assessed for physiological and pathogical changes. Mitochondrial respiratory activity was then assessed in wild-type and knockout animals vessels and isolated cells for their reliance on oxidative and glycolytic metabolism. During atherogenesis, we find that Pink1 knockout affects development of plaque quality rather than plaque quantity by decreasing VSMC and extracellular matrix components, collagen and elastin. Pink1 protein is important in the wild-type VSMC response to metabolic stress and induced a compensatory increase in hexokinase II, which catalyses the first irreversible step in glycolysis. Pink1 appears to play an important role in VSMC energetics during atherogenesis but may also provide insight into the understanding of mitochondrial energetics in other diseases where the regulation of energetic switching between oxidative and glycolytic metabolism is found to be important.

scholarly journals An epithelial scatter factor released by embryo fibroblasts

1985 ◽  
Vol 77 (1) ◽  
pp. 209-223 ◽  
Author(s):  
M. Stoker ◽  
M. Perryman
Keyword(s):  
Epithelial Cells ◽  
Cell Shape ◽  
Mdck Cells ◽  
Physiological Role ◽  
Culture Conditions ◽  
Isolated Cells ◽  
Scatter Factor ◽  
Scattering Factor ◽  
Embryo Fibroblasts ◽  
Factor Separation

Medium conditioned by human embryo fibroblasts breaks structural junctions between several types of epithelial cells, leading to separation and scattering of the cells. An assay developed in MDCK cells shows activity up to a dilution of at least 1 in 64, equivalent to less than 100 ng of total protein. The activity is non-dialysable, heat-labile, and sensitive to trypsin, and it is assumed to be due to one or more proteins. After addition of the factor, separation of MDCK cells begins in about 15 min and is complete in 10 h. It increases migration of MDCK cells into wounds, and causes collapse of domes. Locomotion of isolated cells is not enhanced, but cell shape is affected by local membrane movement. Under the culture conditions used the factor, or an associated protein, causes a weak inhibition of cell growth without cytotoxic activity. The scattering factor has not been purified, nor has a physiological role been identified, but it might be concerned in the mobilization of epithelial cells.

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