A comprehensive survey on optimal components of extracellular matrix for kidney development 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.

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Regulation of human lung fibroblast phenotype and function by vitronectin and vitronectin integrins

Journal of Cell Science ◽

10.1242/jcs.114.19.3507 ◽

2001 ◽

Vol 114 (19) ◽

pp. 3507-3516 ◽

Cited By ~ 1

Author(s):

Amelia K. Scaffidi ◽

Yuben P. Moodley ◽

Markus Weichselbaum ◽

Philip J. Thompson ◽

Darryl A. Knight

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Monoclonal Antibodies ◽

Human Lung ◽

Stress Fibers ◽

Collagen Gels ◽

Human Lung Fibroblast ◽

Myofibroblast Phenotype ◽

And Function ◽

Blocking Antibodies

Myofibroblasts, characterised by high expression of α-smooth muscle actin (α-SMA), are important and transient cells in normal wound healing but are found in increased number in various pathological conditions of the lung including asthma and pulmonary fibrosis. The mechanisms that regulate the myofibroblast phenotype are unknown but are likely to involve signals from the extracellular matrix transmitted via specific integrins. Vitronectin is a glycoprotein released during inflammation and has been shown to regulate the phenotype of vascular smooth muscle cells via αv and β1 integrins. In the current study we have examined whether vitronectin influences the phenotype and function of normal human lung fibroblasts (HFL-1). Incubation of HFL-1 cells with vitronectin induced a concentration-dependent reduction in α-SMA expression. By contrast, function-blocking monoclonal antibodies to the vitronectin integrins αv, β1, αvβ3 and αvβ5 induced the expression of α-SMA and its organization into stress fibers. Expression of α-SMA induced by all function-blocking monoclonal antibodies was abrogated by inhibition of protein kinase C and phosphatidylinositol-3 kinase, but the effects of inhibition of other signalling pathways was integrin dependent. Exposure to other extracellular matrix proteins such as fibronectin, collagen or their integrins did not influence expression of α-SMA. The expression and organization of α-SMA induced by exposure to function-blocking antibodies was translated into an augmented capacity of HFL-1 cells to contract fibroblast populated collagen gels. By contrast, contraction of collagen gels following incubation with vitronectin was not significantly different to control. This study has shown that vitronectin influences the phenotype and behaviour of HFL-1 cells by downregulating the expression of α-SMA and reducing their contractile ability. By contrast, occupancy of specific integrins by function-blocking antibodies upregulated the expression of α-SMA and induced the formation of functional stress fibers capable of contracting collagen gels. These results suggest that vitronectin modulates the fibroblast-myofibroblast phenotype, implying an important role in the remodelling process during lung development or response to injury.

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Abstract 094: Pappa2 is Important for Determining the Nephron Number

Hypertension ◽

10.1161/hyp.68.suppl_1.094 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Vikash Kumar ◽

Chun Yang ◽

Aron M Geurts ◽

Mingyu Liang ◽

Allen W Cowley

Keyword(s):

Mrna Expression ◽

Kidney Development ◽

Brown Norway ◽

Ureteric Bud ◽

Induced Hypertension ◽

Allele Variant ◽

Rat Strain ◽

Nephron Development ◽

And Function ◽

Igfbp 3

Pappa2 is a metalloproteinase which specifically cleaves IGFBP-3 and IGFBP-5 and in turn releases IGF-1. Recently, we have shown that a subcongenic Dahl salt-sensitive (SS) rat strain containing a 0.71 Mbp of chromosome 13 which includes Pappa2 gene from salt-insensitive Brown Norway (26-P strain) is protected significantly (24 mmHg) from salt-induced hypertension (Cowley et al., 2016). Although it is recognized that Pappa2 modulates development of bone size, cranial cartilage and angiogenesis, its role in kidney development and function is unknown. The present study determined the contribution of Pappa2 to nephron development by comparing SS and 26-P rat strains. It was found that Pappa2 mRNA expression was 5-fold higher in embryonic kidney (day 20.5) of the salt-resistant 26-P rats compared with age-matched SS rats. Pappa2 mRNA expression significantly increased with age of kidney reaching a maximum at postnatal day 5 in both strains. Pappa2 mRNA expression at postnatal day 15 was found to be 9-fold higher in the kidney of 26-P compared with SS strain. Immunohistochemistry studies revealed that Pappa2 co-localized with IGFBP-5 in the ureteric bud indicating that Pappa2 could be important for ureteric branching and nephron endowment. Glomerulus/mm 2 was therefore determined by counting total number of glomeruli in kidney sections from pups starting from P0 to P20. The salt-resistant 26-P congenic strain exhibited significantly greater nephron density 9.03 and 7.07 glo/mm 2 compared to 6.89 and 4.85 glo/mm 2 in SS rat at day P15 and P20, respectively. It appears that the Brown Norway pappa2 allele variant prevents the reduced nephron numbers observed in SS rats and thereby protects these congenic rats from salt-induced hypertension.

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Secretion pattern, ultrastructural localization and function of extracellular matrix molecules involved in eggshell formation

Matrix Biology ◽

10.1016/s0945-053x(00)00128-1 ◽

2001 ◽

Vol 19 (8) ◽

pp. 793-803 ◽

Cited By ~ 88

Author(s):

Maria Soledad Fernandez ◽

Alejandra Moya ◽

Luis Lopez ◽

Jose Luis Arias

Keyword(s):

Extracellular Matrix ◽

Ultrastructural Localization ◽

Eggshell Formation ◽

Extracellular Matrix Molecules ◽

And Function

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The Effects of Ionising and Non-Ionising Electromagnetic Radiation on Extracellular Matrix Proteins

Cells ◽

10.3390/cells10113041 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3041

Author(s):

Ren Jie Tuieng ◽

Sarah H. Cartmell ◽

Cliona C. Kirwan ◽

Michael J. Sherratt

Keyword(s):

Extracellular Matrix ◽

Electromagnetic Radiation ◽

Cell Biology ◽

Biological Effects ◽

Well Being ◽

Ecm Proteins ◽

Clinical Consequences ◽

Radiation Induced ◽

And Function ◽

Cellular Components

Exposure to sub-lethal doses of ionising and non-ionising electromagnetic radiation can impact human health and well-being as a consequence of, for example, the side effects of radiotherapy (therapeutic X-ray exposure) and accelerated skin ageing (chronic exposure to ultraviolet radiation: UVR). Whilst attention has focused primarily on the interaction of electromagnetic radiation with cells and cellular components, radiation-induced damage to long-lived extracellular matrix (ECM) proteins has the potential to profoundly affect tissue structure, composition and function. This review focuses on the current understanding of the biological effects of ionising and non-ionising radiation on the ECM of breast stroma and skin dermis, respectively. Although there is some experimental evidence for radiation-induced damage to ECM proteins, compared with the well-characterised impact of radiation exposure on cell biology, the structural, functional, and ultimately clinical consequences of ECM irradiation remain poorly defined.

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The Relationship between Protein Structure and Function: a Comprehensive Survey with Application to the Yeast Genome

10.21236/ada472211 ◽

1999 ◽

Author(s):

Hedi Hegyi ◽

Mark Gerstein

Keyword(s):

Protein Structure ◽

Structure And Function ◽

Yeast Genome ◽

Protein Structure And Function ◽

Comprehensive Survey ◽

And Function ◽

The Relationship

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Agrin is required for survival and function of monocytic cells

Blood ◽

10.1182/blood-2011-09-382812 ◽

2012 ◽

Vol 119 (23) ◽

pp. 5502-5511 ◽

Cited By ~ 21

Author(s):

Cristina Mazzon ◽

Achille Anselmo ◽

Cristiana Soldani ◽

Javier Cibella ◽

Cristina Ploia ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Synapse Formation ◽

Myeloid Cell ◽

Heparan Sulfate Proteoglycans ◽

Extracellular Matrix Protein ◽

Monocytic Cells ◽

Hematopoietic System ◽

Extracellular Signal ◽

And Function

Abstract Agrin, an extracellular matrix protein belonging to the heterogeneous family of heparan sulfate proteoglycans (HSPGs), is expressed by cells of the hematopoietic system but its role in leukocyte biology is not yet clear. Here we demonstrate that agrin has a crucial, nonredundant role in myeloid cell development and functions. We have identified lineage-specific alterations that affect maturation, survival and properties of agrin-deficient monocytic cells, and occur at stages later than stem cell precursors. Our data indicate that the cell-autonomous signals delivered by agrin are sensed by macrophages through the α-DC (DG) receptor and lead to the activation of signaling pathways resulting in rearrangements of the actin cytoskeleton during the phagocytic synapse formation and phosphorylation of extracellular signal-regulated kinases (Erk 1/2). Altogether, these data identify agrin as a novel player of innate immunity.

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