Role of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Light-Induced Photoreceptor Degeneration in Mouse Retina

Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) is a potent mitogen for smooth-muscle cells (SMCs) belonging to the EGF family. We have previously determined that HB-EGF is expressed in macrophages and SMCs of human atherosclerotic lesions and that its membrane-anchored precursor, proHB-EGF, also has a juxtacrine mitogenic activity which is markedly enhanced by CD9, a surface marker of lymphohaemopoietic cells. Therefore, when both proHB-EGF and CD9 are expressed on macrophages, they may strongly promote the development of atherosclerosis. In the present study we have investigated the changes in proHB-EGF and CD9 in THP-1 cells during differentiation into macrophages and by the addition of oxidized low-density lipoproteins (OxLDL) and assessed juxtacrine growth activity of THP-1 macrophages for human aortic SMCs. HB-EGF and CD9 at both the mRNA and the protein level were up-regulated after differentiation into macrophages, and further expression of HB-EGF was induced by the addition of OxLDL or lysophosphatidylcholine. Juxtacrine induction by formalin-fixed growth was suppressed to control levels by an inhibitor of HB-EGF and was partially decreased by anti-CD9 antibodies. These results suggest that co-expression of proHB-EGF and CD9 on macrophages plays an important role in the development of atherosclerosis by a juxtacrine mechanism.

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Role of heparin-binding epidermal growth factor–like growth factor as a hepatotrophic factor in rat liver regeneration after partial hepatectomy

Hepatology ◽

10.1002/hep.1840220535 ◽

1995 ◽

Vol 22 (5) ◽

pp. 1584-1590 ◽

Cited By ~ 1

Author(s):

Shinichi Kiso ◽

Sumio Kawata ◽

Shinji Tamura ◽

Shigeki Higashiyama ◽

Nobuyuki Ito ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Liver Regeneration ◽

Partial Hepatectomy ◽

Rat Liver ◽

Heparin Binding ◽

Rat Liver Regeneration ◽

Epidermal Growth

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Possible pro-inflammatory role of heparin-binding epidermal growth factor-like growth factor in the active phase of systemic sclerosis

The Journal of Dermatology ◽

10.1111/1346-8138.14088 ◽

2017 ◽

Vol 45 (2) ◽

pp. 182-188

Author(s):

Megumi Hirabayashi ◽

Yoshihide Asano ◽

Takashi Yamashita ◽

Shunsuke Miura ◽

Kouki Nakamura ◽

...

Keyword(s):

Systemic Sclerosis ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Active Phase ◽

Heparin Binding ◽

Epidermal Growth

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Role of membrane-bound heparin-binding epidermal growth factor-like growth factor (HB-EGF) in renal epithelial cell branching

Kidney International ◽

10.1046/j.1523-1755.2002.00358.x ◽

2002 ◽

Vol 61 (6) ◽

pp. 1968-1979 ◽

Cited By ~ 21

Author(s):

Tsukasa Takemura ◽

Satoshi Hino ◽

Mituru Okada ◽

Yuka Murata ◽

Hidehiko Yanagida ◽

...

Keyword(s):

Growth Factor ◽

Epithelial Cell ◽

Epidermal Growth Factor ◽

Heparin Binding ◽

Renal Epithelial Cell ◽

Epidermal Growth ◽

Membrane Bound

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Autocrine Regulation of Keratinocytes: The Emerging Role of Heparin-Binding, Epidermal Growth Factor-Related Growth Factors

Journal of Investigative Dermatology ◽

10.1046/j.1523-1747.1998.00390.x ◽

1998 ◽

Vol 111 (5) ◽

pp. 715-721 ◽

Cited By ~ 96

Author(s):

Michael Piepkorn ◽

Mark R. Pittelkow ◽

Paul W. Cook

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Heparin Binding ◽

Autocrine Regulation ◽

Epidermal Growth

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A positively charged cluster in the epidermal growth factor-like domain of Factor VII-activating protease (FSAP) is essential for polyanion binding

Biochemical Journal ◽

10.1042/bj20051563 ◽

2006 ◽

Vol 394 (3) ◽

pp. 687-692 ◽

Cited By ~ 26

Author(s):

Boran Altincicek ◽

Aya Shibamiya ◽

Heidi Trusheim ◽

Eleni Tzima ◽

Michael Niepmann ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Three Dimensional ◽

Factor Vii ◽

Dimensional Structure ◽

Heparin Binding ◽

Interaction Sites ◽

Interaction Domains ◽

Epidermal Growth

FSAP (Factor VII-activating protease) is a novel plasma-derived serine protease that regulates haemostasis as well as vascular cell proliferation. FSAP undergoes autoactivation in the presence of polyanionic macromolecules such as heparin and RNA. Competition experiments suggest that RNA and heparin bind to the same or overlapping interaction sites. A proteolysis approach, where FSAP was hydrolysed into smaller fragments, was used to identify the polyanion-binding site. The EGF (epidermal growth factor)-like domains EGF2 and EGF3 of FSAP are the major interaction domains for RNA. The amino acids Arg170, Arg171, Ser172 and Lys173 within the EGF3 domain were essential for this binding. This is also the region with the highest positive net charge in the protein and is most probably located in an exposed loop. It is also highly conserved across five species. Disruption of disulphide bridges led to the loss of RNA and heparin binding, indicating that the three-dimensional structure of the EGF3 domain is essential for binding to negatively charged heparin or RNA. The identification of polyanion-binding sites will help to define the role of FSAP in the vasculature.

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