scholarly journals Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages

1997 ◽  
Vol 328 (3) ◽  
pp. 923-928 ◽  
Author(s):  
Noriyuki OUCHI ◽  
Shinji KIHARA ◽  
Shizuya YAMASHITA ◽  
Shigeki HIGASHIYAMA ◽  
Tsutomu NAKAGAWA ◽  
...  

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.

2004 ◽  
Vol 18 (8) ◽  
pp. 2035-2048 ◽  
Author(s):  
Bukhtiar H. Shah ◽  
Akin Yesilkaya ◽  
J. Alberto Olivares-Reyes ◽  
Hung-Dar Chen ◽  
László Hunyady ◽  
...  

1999 ◽  
Vol 19 (3) ◽  
pp. 307-320 ◽  
Author(s):  
Nobutaka Kawahara ◽  
Kazuhiko Mishima ◽  
Shigeki Higashiyama ◽  
Naoyuki Taniguchi ◽  
Akira Tamura ◽  
...  

The functions of the epidermal growth factor (EGF) family members in the adult brain are not known. This study investigated the changes in the expression of members of the EGF family following global ischemia employing in situ hybridization and immunohistochemical techniques to elucidate their roles in pathological conditions. EGF mRNA was not detected in either the control or the postischemic rat brain. Although transforming growth factor-α (TGF-α) mRNA was widely expressed in the normal brain, its expression did not change appreciably following ischemia. By contrast, heparin-binding EGF-like growth factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not show any increase prior to ischemic neuronal injury in the CA1 sector, the region most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the postischemic brain suggested a slight increase of immunostaining in the dentate gyrus of the hippocampus and the cortex. These findings showed that the gene encoding HB-EGF is stress-inducible, indicating the like-lihood that HB-EGF is a neuroprotective factor in cerebral ischemia.


2013 ◽  
Vol 54 (6) ◽  
pp. 3815 ◽  
Author(s):  
Yuki Inoue ◽  
Kazuhiro Tsuruma ◽  
Tomohiro Nakanishi ◽  
Atsushi Oyagi ◽  
Yuta Ohno ◽  
...  

Hepatology ◽  
1995 ◽  
Vol 22 (5) ◽  
pp. 1584-1590 ◽  
Author(s):  
Shinichi Kiso ◽  
Sumio Kawata ◽  
Shinji Tamura ◽  
Shigeki Higashiyama ◽  
Nobuyuki Ito ◽  
...  

2017 ◽  
Vol 45 (2) ◽  
pp. 182-188
Author(s):  
Megumi Hirabayashi ◽  
Yoshihide Asano ◽  
Takashi Yamashita ◽  
Shunsuke Miura ◽  
Kouki Nakamura ◽  
...  

2002 ◽  
Vol 61 (6) ◽  
pp. 1968-1979 ◽  
Author(s):  
Tsukasa Takemura ◽  
Satoshi Hino ◽  
Mituru Okada ◽  
Yuka Murata ◽  
Hidehiko Yanagida ◽  
...  

2006 ◽  
Vol 394 (3) ◽  
pp. 687-692 ◽  
Author(s):  
Boran Altincicek ◽  
Aya Shibamiya ◽  
Heidi Trusheim ◽  
Eleni Tzima ◽  
Michael Niepmann ◽  
...  

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.


2002 ◽  
Vol 297 (2) ◽  
pp. 375-381 ◽  
Author(s):  
Nobuyoshi Tanaka ◽  
Katsuhiko Masamura ◽  
Masahiro Yoshida ◽  
Masayuki Kato ◽  
Yasuyuki Kawai ◽  
...  

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