Chest
Clinical Implications of Basic ResearchFibronectin: A Versatile Matrix Protein with Roles in Thoracic Development, Repair and Infection
Section snippets
Fibronectin Biochemistry
Fibronectins are dimeric glycoproteins of approximately 500 kDa molecular weight which are derived from the variable splicing of a single gene product. Fibronectins are strikingly modular proteins composed of protease-resistant domains which retain their individual activities following cleavage and purification from the intact molecule (Fig. 1, top). These protease-resistant domains are in turn composed of smaller homologous motifs termed type I, II and III repeats which comprise the majority
Fibronectin Receptors
Cells interact with fibronectin via specific cell surface receptors (Fig. 1, bottom).1 Fibronectin receptors include members of the integrin family, a structurally related group of transmembrane heterodimeric glycoproteins conserved during evolution and responsible for cell binding to extracellular matrices or to other cells.17 Integrin receptors are composed of distinct a subunits that help confer ligand binding specificity and β subunits common to other integrins. Traditionally, integrins
Biological Actions of Fibronectin
The initial interaction of cells with immobilized fibronectin is the binding of cell surface fibronectin receptors to adhesive sequences contained within the fibronectin molecule. This binding event activates multiple intracellular processes responsible for cell adhesion and subsequent cell spreading. Many of these intracellular activities are mediated via the integrin VLA-5. Following binding to fibronectin, VLA-5 receptors aggregate or cluster into membrane structures termed adhesive plaques
Fibronectin in Thoracic Development
Human embryogenesis is characterized by remarkable morphologic changes resulting in the formation of specialized tissues. Intricate regulation of biologic events such as cell adhesion, migration, cytodifferentiation and proliferation is essential for the normal progression of organogenesis. As described earlier, fibronectin is highly expressed in embryonic tissues and has been shown to affect many of the cellular processes required for embryogenesis in vitro.4,25,30 It is therefore not
Fibronectin in Lung Repair and Fibrosis
Acute lung injury is characterized by interstitial edema, formation of alveolar exudates, disruption of basement membranes and tissue invasion by inflammatory cells.39 In general, regardless of the causative agent, the lung responds in a stereotypical manner. Pulmonary injury caused by such diverse agents as smoke, acid, drugs or multiorgan disease results in a generalized activation of counterreactive mechanisms responsible for ridding the lung of the injurious agents and effecting tissue
Fibronectin in Cardiopulmonary Infection
Adherence of microorganisms to host epithelial surfaces is necessary for the establishment of infection in the skin, urinary system and upper and lower respiratory tracts. Microorganisms have evolved widely varied mechanisms to attach to host epithelial cells including specialized structures such as pili and fimbriae. Recently, it has been found that some microbes also may exploit host adhesive proteins, such as fibronectin, to attach to epithelial surfaces. Following adhesion and local
Current and Future Research
Although much has been learned of fibronectin's structure, function and potential role in disease, several important topics provide the basis for ongoing investigation. The control of fibronectin expression continues to be an area of active research. Recent investigations have led to cloning of the fibronectin gene and promoter.71, 72 Study of these sequences will provide further insight into the control of fibronectin gene expression and may eventually lead to novel therapeutic approaches to
Summary
Fibronectin, a dimeric glycoprotein, utilizes its multidomained structure to interact with components of the extracellular matrix, microorganisms and mesenchymal, epithelial and inflammatory cells. Fibronectin interacts with these cells through specific cell surface receptors including members of the integrin family which mediate many of fibronectin's effects on cellular function such as promotion of cell adhesion, proliferation, migration and cytodifferentiation. These varied biologic
References (71)
- et al.
Analysis of local mRNA expression for extracellular matrix proteins and growth factors using in-situ hybridization in fibroproliferative lung disorders
Chest
(1991) - et al.
Fibronectin's amino-terminal matrix assembly site is located within the 29kDa amino-terminal domain containing five type I repeats
J Biol Chem
(1988) - et al.
Transforming growth factor-β stimulates the expression of fibronectin and both subunits of the human fibronectin receptor by cultured human lung fibroblasts
J Biol Chem
(1988) - et al.
Identification of a murine Peyer's patch-specific lymphocyte homing receptor as an integrin molecule with an A chain homologous to VLA-4
Cell
(1989) - et al.
Cell surface molecules that bind fibronectin's matrix assembly domain
J Biol Chem
(1991) - et al.
Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation
Cell
(1987) - et al.
A role for fibronectin in the migration of avian precardiac cells: II. rotation of the heart-forming region during different stages and its effects
Dev Biol
(1988) - et al.
A role for fibronectin in the migration of avian precardiac cells: I. dose dependent effects of fibronectin antibody
Dev Biol
(1988) - et al.
Reagents that inhibit fibronectin matrix assembly of cultured cells also inhibit lung branching morphogenesis in vitro: implications for lung development, injury, and repair
Chest
(1991) Role of transforming growth factor-β in repair and fibrosis
Chest
(1991)
Isolation and characterization of a fibronectin receptor from Staphylococcus aureus
J Biol Chem
Fibronectin mediates attachment of Staphylococcus aureus to human neutrophils
Blood
Fibronectin and its receptors
Ann Rev Biochem
Extracellular matrix assembly
Ann Rev Cell Biol
Physiology of fibronectin
Ann Rev Med
Fibronectin in early amphibian embryos: migrating mesodermal cells contact fibronectin established prior to gastrulation
Cell Tissue Res
Human alveolar macrophage fibronectin: synthesis, secretion, and ultrastructural localization during gelatin-coated latex particle binding
J Cell Biol
Immunohistochemical detection of architectural changes and fibroblasts phenotype in human pulmonary fibrosis
Am Rev Respir Dis
Bronchovascular fibronectin in smokers and nonsmokers
Am Rev Respir Dis
Lung extracellular matrix: physiology and pathophysiology
Hosp Pract
Molecular biology of fibronectin
Ann Rev Cell Biol
Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin
J Cell Biol
Comparative studies on amniotic and plasma fibronectin's
Biochem J
Expression of the fibronectin gene
Am J Respir Cell Mol Biol
New perspectives in cell adhesion: RGD and integrins
Science
Integrins and other cell adhesion molecules
The FASEB J
Receptors for extracellular matrix components
Am J Physiol
Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton
Ann Rev Cell Biol
Analysis of fibronectin receptor function with monoclonal antibodies: roles in cell adhesion, migration, matrix assembly and cytoskeleton organization
J Cell Biol
The fibronectin receptor is organized by extracellular matrix fibronectin: implications for oncogenic transformation and for cell recognition of fibronectin matrices
J Cell Biol
Fibronectins
Role of fibronectin as a growth factor for fibroblasts
J Cell Biol
Fibronectin-plasma membrane interaction in the adhesion of hematopoietic cells
J Cell Biol
Signal transduction through the fibronectin receptor induces collagenase and stromolysin gene expression
J Cell Biol
Cited by (104)
Time-resolved proteome and transcriptome of paraquat-induced pulmonary fibrosis
2022, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :FN1 is one of the classic fibrosis marker genes. It serves as an adhesive substrate and promotes cell proliferation and differentiation [22]. S100A4 is a small Ca2+ binding protein and is considered as a fibroblast marker in tissue remodeling processes [23,24].
Neonatal Pulmonary Host Defense
2017, Fetal and Neonatal Physiology, 2-Volume SetPredisposition for disrepair in the aged lung
2012, American Journal of the Medical SciencesCitation Excerpt :In clinical and experimental forms of acute and chronic lung injury, there is increased expression of extracellular matrix components such as Fn.24 Fn is a matrix glycoprotein that affects many cellular processes, including adhesion, migration, proliferation and differentiation and is a sensitive marker of activation of tissue remodeling.6,24,25 In injured lungs, deposition of Fn is believed to accelerate the re-epithelialization of denuded basement membranes25 and increase the proliferation of fibroblasts.26
Neonatal Pulmonary Host Defense
2011, Fetal and Neonatal Physiology E-Book, Fourth EditionThe outer wall of small airways is a major site of remodeling in fatal asthma
2009, Journal of Allergy and Clinical ImmunologyCitation Excerpt :In this case airway remodeling would represent a process used to overcome increased instability of the bronchial tree. Fibronectin is a matrix protein that is highly expressed in injured tissues, with multiple biologic functions in tissue repair, including the control of ECM deposition and organization.35,36 In the present study the increased fibronectin content in fatal asthma was localized to the OA of small airways and might be associated with collagen changes at this site.
This work was supported in part by funds from the American Heart Association (Clinician-Scientist Award No. 91004230 to A.H.L.) and by a Minority Medical Faculty Development Award from The Robert Wood Jonnson Foundation (to Dr. Roman).