Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

Inhibition of Angiogenesis and Vascular Leakiness by Angiopoietin-Related Protein 4

Abstract: Angiopoietins and angiopoietin-related proteins (ARPs) have been shown to regulate angiogenesis, a process essential for various neovascular diseases including tumors. Here, we identify ARP4/fasting-induced adipose factor/peroxisome proliferator-activated receptor γ angiopoietin-related as a novel antiangiogenic modulatory factor. We hypothesized that ARP4 may regulate angiogenesis. In vitro experiments using purified recombinant ARP4 protein revealed that ARP4 markedly inhibited the proliferation, chemotaxis, and tubule formation of endothelial cells. Moreover, using corneal neovascularization and Miles permeability assays, we found that both vascular endothelial growth factor-induced in vivo angiogenesis and vascular leakiness were significantly inhibited by the addition of ARP4. Finally, we found remarkable suppression of tumor growth within the dermal layer associated with decreased numbers of invading blood vessels in transgenic mice that express ARP4 in the skin driven by the keratinocyte promoter. These findings demonstrate that ARP4 functions as a novel antiangiogenic modulatory factor and indicate a potential therapeutic effect of ARP4 in neoplastic diseases.

Molecular cloning and expression of the human interleukin 5 receptor.

Abstract: Human interleukin 5 (IL-5) plays an important role in proliferation and differentiation of human eosinophils. We report the isolation of cDNA clones from cDNA libraries of human eosinophils by using murine IL-5 receptor alpha chain cDNA as a probe. Analysis of the predicted amino acid sequence indicated that the human IL-5 receptor has approximately 70% amino acid sequence homology with the murine IL-5 receptor and retains features common to the cytokine receptor superfamily. One cDNA clone encodes a glycoprotein of 420 amino acids (Mr 47,670) with an NH2-terminal hydrophobic region (20 amino acids), a glycosylated extracellular domain (324 amino acids), a transmembrane domain (21 amino acids), and a cytoplasmic domain (55 amino acids). Another cDNA encodes only the extracellular domain of this receptor molecule. Other cDNA clones encode molecules having diversified cytoplasmic domains. COS7 cells transfected with the cDNA expressed a approximately 60-kD protein and bound IL-5 with a single class of affinity (Kd = 250-590 pM). The Kd values were similar to that observed in normal human eosinophils. In contrast to the murine 60-kD alpha chain, which binds IL-5 with low affinity (Kd = approximately 10 nM), the human alpha chain homologue can bind IL-5 with much higher affinity by itself. RNA blot analysis of human cells demonstrated two transcripts (approximately 5.3 and 1.4 kb). Both of them were expressed in normal human eosinophils and in erythroleukemic cell line TF-1, which responds to IL-5. The human IL-5 receptor characterized in this paper is essential for signal transduction, because expression of this molecule in murine IL-3-dependent cell line FDC-P1 allowed these cells to proliferate in response to IL-5.