scholarly journals Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling

2021 ◽  
Vol 22 (4) ◽  
pp. 2198
Author(s):  
Hyunbum Kim ◽  
Laurensia Danis Anggradita ◽  
Sun-Jae Lee ◽  
Sung Sik Hur ◽  
Joonsuk Bae ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Traction Force ◽  
Dermal Fibroblasts ◽  
Cross Linking ◽  
Ecm Remodeling ◽  
Cell Matrix ◽  
Epidermal Growth ◽  
Collagen Cross Linking

Keloid and hypertrophic scars are skin fibrosis-associated disorders that exhibit an uncontrollable proliferation of fibroblasts and their subsequent contribution to the excessive accumulation of extracellular matrix (ECM) in the dermis. In this study, to elucidate the underlying mechanisms, we investigated the pivotal roles of epidermal growth factor (EGF) in modulating fibrotic phenotypes of keloid and hypertrophic dermal fibroblasts. Our initial findings revealed the molecular signatures of keloid dermal fibroblasts and showed the highest degree of skin fibrosis markers, ECM remodeling, anabolic collagen-cross-linking enzymes, such as lysyl oxidase (LOX) and four LOX-like family enzymes, migration ability, and cell–matrix traction force, at cell–matrix interfaces. Furthermore, we observed significant EGF-mediated downregulation of anabolic collagen-cross-linking enzymes, resulting in amelioration of fibrotic phenotypes and a decrease in cell motility measured according to the cell–matrix traction force. These findings offer insight into the important roles of EGF-mediated cell–matrix interactions at the cell–matrix interface, as well as ECM remodeling. Furthermore, the results suggest their contribution to the reduction of fibrotic phenotypes in keloid dermal fibroblasts, which could lead to the development of therapeutic modalities to prevent or reduce scar tissue formation.

Receptors for epidermal growth factor and insulin-like growth factor-I on preimplantation trophoderm of the pig

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 221-227
Author(s):  
A.N. Corps ◽  
D.R. Brigstock ◽  
C.J. Littlewood ◽  
K.D. Brown
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Molecular Mass ◽  
Cross Linking ◽  
Relative Molecular Mass ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Epidermal Growth ◽  
Growth Factor I

125I-labelled epidermal growth factor (125I-EGF) and 125I-labelled insulin-like growth factor-I (125I-IGF-I) bound to trophoderm cells from pig blastocysts obtained on days 15–19 of pregnancy. Specific binding was detected on freshly isolated cell suspensions and on cells cultured for several days. The binding of 125I-EGF was inhibited by increasing concentrations of EGF, but not by various other growth factors and hormones. Chemical cross-linking of 125I-EGF to its receptors using disuccinimidyl suberate (DSS) revealed a radiolabelled band of relative molecular mass 160,000, similar to that identified as the EGF receptor in other cell types. The binding of 125I-IGF-I was inhibited by both IGF-I and insulin, indicating that the receptors were either type I IGF receptors or insulin receptors. Cross-linking of 125I-IGF-I to serum-free supernatants from trophoderm cultures showed that the cells secreted an IGF-binding protein, giving a complex of relative molecular mass about 45,000. The presence of receptors for EGF and IGF/insulin suggests that these factors could be involved in regulating the growth and development of the early blastocyst.

scholarly journals Structural Evidence for Loose Linkage between Ligand Binding and Kinase Activation in the Epidermal Growth Factor Receptor

2010 ◽  
Vol 30 (22) ◽  
pp. 5432-5443 ◽  
Author(s):  
Chafen Lu ◽  
Li-Zhi Mi ◽  
Michael J. Grey ◽  
Jieqing Zhu ◽  
Elizabeth Graef ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Transmembrane Domains ◽  
Cross Linking ◽  
Hydrophobic Domain ◽  
Kinase Activation ◽  
Epidermal Growth

ABSTRACT The mechanisms by which signals are transmitted across the plasma membrane to regulate signaling are largely unknown for receptors with single-pass transmembrane domains such as the epidermal growth factor receptor (EGFR). A crystal structure of the extracellular domain of EGFR dimerized by epidermal growth factor (EGF) reveals the extended, rod-like domain IV and a small, hydrophobic domain IV interface compatible with flexibility. The crystal structure and disulfide cross-linking suggest that the 7-residue linker between the extracellular and transmembrane domains is flexible. Disulfide cross-linking of the transmembrane domain shows that EGF stimulates only moderate association in the first two α-helical turns, in contrast to association throughout the membrane over five α-helical turns in glycophorin A and integrin. Furthermore, systematic mutagenesis to leucine and phenylalanine suggests that no specific transmembrane interfaces are required for EGFR kinase activation. These results suggest that linkage between ligand-induced dimerization and tyrosine kinase activation is much looser than was previously envisioned.

scholarly journals Localization of a major receptor-binding domain for epidermal growth factor by affinity labeling.

1988 ◽  
Vol 8 (4) ◽  
pp. 1831-1834 ◽  
Author(s):  
I Lax ◽  
W H Burgess ◽  
F Bellot ◽  
A Ullrich ◽  
J Schlessinger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Cross Linking ◽  
Receptor Binding Domain ◽  
Site Specific ◽  
Entire Sequence ◽  
Epidermal Growth ◽  
Domain Iii ◽  
Amino Acid Sequence Conservation

Epidermal growth factor (EGF) receptor was affinity labeled with 125I-labeled EGF, using bifunctional covalent cross-linking agents. The affinity-labeled receptor was isolated and cleaved with CNBr to yield a single-labeled fragment, which was unequivocally identified by site-specific antibodies and other methods to encompass residues 294 to 543 of the EGF receptor. On the basis of amino acid sequence conservation, the extracellular portion of EGF receptor can be divided into four domains. The labeled CNBr fragment contains the entire sequence which is flanked by the two cysteine-rich domains of extracellular portion of the EGF receptor denoted as domain III. On the basis of these and other results, we propose that domain III contributes most of the interactions that define ligand-binding specificity of the EGF receptor.

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