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R I Hata

Publications and source records attributed to R I Hata.

12 recordsLinked to original sources
PubMed2001

Induction of SPARC by VEGF in human vascular endothelial cells.

SPARC/osteonectin/BM-40 is a matricellular protein that is thought to be involved in angiogenesis and endothelial barrier function. Previously, we have detected high levels of SPARC expression in endothelial cells (ECs) adjacent to carcinomas of kidney and tongue. Although SPARC-derived peptide showed an angiogenic effect, intact SPARC itself inhibited the mitogenic activity of vascular endothelial growth factor (VEGF) for ECs by the inhibiting phosphorylation of flt-1 (VEGF receptor 1) and subsequent ERK activation. Thus, the role of SPARC in tumor angiogenesis, stimulation or inhibition, is still unclear. To clarify the role of SPARC in tumor growth and progression, we determined the effect of VEGF on the expression of SPARC in human microvascular EC line, HMEC-1, and human umbilical vein ECs. VEGF increased the levels of SPARC protein and steady-state levels of SPARC mRNA in serum-starved HMEC-1 cells. Inhibitors (SB202190 and SB203580) of p38, a mitogen-activated protein (MAP) kinase, attenuated VEGF-stimulated SPARC production in ECs. Since intact SPARC inhibits phosphorylation ERK MAP kinase in VEGF signaling, it was suggested that SPARC plays a dual role in the VEGF functions, tumor angiogenesis, and extravasation of tumors mediated by the increased permeability of endothelial barrier function.

Cells, Cultured↗
PubMed2001

Activin A induces expression of rat Sel-1l mRNA, a negative regulator of notch signaling, in rat salivary gland-derived epithelial cells.

We previously established a rat submandibular gland (SMG)-derived epithelial cell line (RSMG-1) to study the mechanism of morphogenesis in salivary gland development and regeneration. We found that activin A regulated the branching morphogenesis of RSMG-1 cells, suggesting that it is involved in SMG morphogenesis. We used a subtraction cloning procedure with activin-A-treated and untreated RSMG-1 cells to identify activin-A-induced genes. One of the genes detected encoded a rat homologue of Sel-1l (rSel-1l). rSel-1l is a mammalian homologue of C. elegans sel-1, which is a negative regulator of Notch signaling. In this study, we confirmed that activin A induces rSel-1l mRNA expression in RSMG-1 cells, and that rSel-1l is expressed in SMG acinar cells. These results suggest that activin A regulates the differentiation of RSMG-1 cells to acinar cells.

Activins↗
PubMed1999

Transcriptional regulation of the human type I collagen alpha2 (COL1A2) gene by the combination of two dinucleotide repeats.

Human type I collagen alpha2 (COL1A2) gene has two dinucleotide repeats: one in the 5'-flanking region of the gene is composed of poly(dC-dA) and poly(dC-dG), while the other in the first intron consists of poly(dG-dT). In this study, we show that transcription of the COL1A2 gene is regulated by these repeats. Luciferase reporter gene assay indicated that the transcriptional activity of the COL1A2 gene was enhanced by the co-presence of both repeats, but not by either repeat alone. Analysis of the polymorphism in the two repeat regions indicated that both sequences have a variation in their repetition number, thus showing that these dinucleotide repeats constitute microsatellites. A study using constructs containing various combinations of the repeat alleles showed differences in their transcriptional activities. The results, however, showed that the stimulation rate of luciferase activity was not linear with the repetitive number of the repeats either in the 5' flanking region or in the first intron of the gene and that the stimulation was provided by the combination of these polymorphic repetitive sequences. These observations indicated that the dinucleotide repeats have an enhancing activity on transcription of the COL1A2 gene and that the variation in the number of repetitions may partly be responsible for the difference in the transcriptional activity of the gene.

Alleles↗
PubMed1997

Stimulation of collagen synthesis in rat cardiac fibroblasts by exposure to hypoxic culture conditions and suppression of the effect by natriuretic peptides.

Synthesis of type I and type III collagens by rat cardiac fibroblasts was stimulated when the cells were cultured under 95% N2/5% CO2 for one hour followed by incubation under normoxic conditions for 24 hours. The stimulative effect was attenuated by the presence of atrial natriuretic peptide (ANP, 10(-6) M) or brain natriuretic peptide (BNP, 10 6 M) in the culture medium. Northern blot analysis indicated that alpha1(I) and alpha1(III) collagen mRNA levels were also increased by hypoxia, and decreased with the addition of ANP or BNP in a dose-dependent manner. These results indicate interaction between intracellular signals of a physical stimulus (hypoxic stress) and those of a chemical one (ANP or BNP) and demonstrate that both signals regulate collagen synthesis by cardiac fibroblasts at the levels of the mRNAs. The results also suggest that natriuretic peptides produced by cardiomyocytes in vivo may function as paracrine factors that play a role in the prevention of cardiac fibrosis in ischaemic heart diseases.

Animals↗
PubMed1996

Where am I? How a cell recognizes its positional information during morphogenesis.

Morphogenesis is an old, and one of the latest, fascinating fields in biological science and a huge number of papers on molecular mechanisms underlying it have been published. But most of the works and reviews on these mechanisms pertain to molecules of, as it were, the planning or design of morphogenesis, such as morphogens and homeodomain proteins. In this review, I will describe the function of extracellular matrix (ECM) and other cell adhesion molecules in morphogenesis as that of actual morpho-creating molecules, morphocreators, and discuss their roles as positional information-pertaining molecules.

Animals↗
PubMed1980

Glycosaminoglycan synthesis by liver parenchymal cell clones in culture and its change with transformation.

Albumin-producing rat liver parenchymal cell clones (BB and BC) and their subclones in the confluent culture synthesized heparan sulfate as the major component and dermatan sulfate, chondroitin sulfate and hyaluronic acid as the minor ones. Their relative contents were similar to those present in the rat liver. Analyses of glycosaminoglycans synthesized by subclone cells (BB1S) at various cell densities, cell growth phases and passage levels have shown that relative content of heparan sulfate remained constant, suggesting that the epithelial cell possesses a stable heparan sulfate-producing capacity. On the other hand, the level of hyaluronic acid production was high at low cell density, though it remained constant during cell proliferation. Chemically transformed rat liver parenchymal cells (M) produced relatively higher amount of chondroitin sulfate than non-transformed cells did, as observed with 4-nitroquinoline-1-oxide-transformed 3T3 cells, compared to 3T3 714 cells. The results obtained on this study strongly suggest that the liver parenchymal cells synthesize a major part of the glycosaminoglycans of the liver and chondroitin sulfate production is closely related to cellular proliferations.

Animals↗
PubMed1978

A low-sulfated chondroitin sulfate in rat blood: an acidic glycosaminoglycan with a high metabolic rate.

The rate of metabolism of low-sulfated chondroitin 4-sulfate, a predominant glycosaminoglycan in blood, has been studied by administering intraperitoneally radioactive hexosamine and/or sulfate to rats. The biological half-life of the material was estimated to be 10--12 h, suggesting that the metabolic process of blood low-sulfated chondroitin sulfate is different from that of glycosaminoglycans in the tissue.

Animals↗
PubMed1978

Low-sulfated chondroitin sulfate in human blood and urine.

Blood and urinary low-sulfated chondroitin sulfate from healthy young and aged volunteers have been characterized by gel chromatography, two-dimensional electrophoresis on cellulose acetate strips and by chemical and enzymatic analysis. No difference in content of the material (24 nmol hexosamine per ml plasma) was observed regardless of age. Chemical composition (approximately 40% sulfation at 4-position of galactosamine) and molecular weight (about 8000) of blood and urinary low-sulfated chondroitin sulfates were found to be the same, though urinary excretion of the material was much higher in the aged than in the young adults (Ohkawa et al. (1972) J. Biochem. 72, 1495--1501). Low-sulfated chondroitin sulfate in serum was in a bound form with a molecular weight of more than 100000, irrespective of age. These results suggest that increase in urinary excretion of low-sulfated chondroitin sulfate in the aged is mainly due to renal dysfunction. Low-sulfated chondroitin sulfate was also the main component of acidic glycosaminoglycans in blood from patients with Hurler's syndrome who excreted excessive amounts of dermatan sulfate and heparan sulfate in urine. This suggests that low sulfated chondroitin sulfate in blood is not merely a precursor of urinary glycosaminoglycans in the case of healthy young adults.

Adult↗
PubMed1978

De novo induction of a gene product during heterologous epithelial--mesenchymal interactions in vitro.

Mesenchymal specification of epithelial cytodifferentiation and morphogenesis has been considered to be a general feature of various epithelial-mesenchymal interacting systems (e.g., salivary gland, mammary gland, feather, hair, and tooth morphogenesis). In contrast, we have demonstrated that a mesenchyme can be induced by a heterologous epithelium to synthesize in quantity a specific gene product(s) unorthodox to the organ from which the mesenchyme was taken. Stage 22-23 avian limb bud epithelium induced 17-day embryonic mouse tooth mesenchyme to differentiate into cartilage. Peptide analysis (cyanogen bromide cleavage after purification of extracted collagen chains) demonstrated that heterologous tissue recombinations produced type II collagen [alpha(II)](3) (i.e., cartilage-type) in addition to type I collagen [alpha(I)](2)alpha(2). Intact or reconstituted mouse molar tooth organs synthesized type I collagen and type I trimer [alpha(I)](3) collagen. Immunohistochemical criteria using anti-type II collagen antibodies identified type II collagen in cartilage-like matrix within the mesenchymal component of heterologous tissue recombinants. Cartilage has never been described during in vivo or in vitro tooth tissue differentiation or associated with the pathology of dental papilla mesenchyme. These results support the hypothesis that epithelial-mesenchymal interactions during embryonic development can selectively induce de novo synthesis of unique gene products.

Animals↗
PubMed1977

Specific changes in the collagen phenotype of BALB 3T3 cells as a result of transformation by sarcoma viruses or a chemical carcinogen.

Radioactive proline-labeled procollagen, accumulated during a 3-hr incubation of normal and transformed BALB 3T3 cultures, was treated with pepsin and the resulting collagen components were analyzed by carboxymethyl-cellulose chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis in the presence or absence of reducing agent. Collagen in the medium of three subclones of BALB 3T3 A-31 that exhibited contact-inhibition of growth at confluence, as well as in the medium of one that did not, consisted of alpha(1) and alpha(2) subunits in the ratio of 3:1, suggesting that 3T3 cells synthesize type I collagen, [alpha(1)(I)](2)alpha(2), and another type, which we have designated X, composed of alpha(1) chains, which may or may not be identical to alpha(1)(I). Culture medium from 3T3 transformed by Kirsten or Moloney sarcoma virus contained type I collagen and another type differing from I and X and designated as type Y. The latter appeared to be similar to type III collagen [alpha(1)(III)](3), since it contained intrahelical disulfide bonds. Analysis of intracellular collagen also demonstrated the presence of type III in Ki-3T3 and its absence from 3T3 cells. Collagen components from the medium of a simian virus 40 transformant were identical to those of the contact-inhibited clones, while the collagen from a 4-nitroquinoline-1-oxide-induced transformant was composed mainly of two components differing from alpha(1)(I), alpha(2), or alpha(1)(III). These results suggest that the type of collagen accumulated in transformed cell cultures may be specifically related to the transforming agent.

4-Nitroquinoline-1-oxide↗