Search PubMed⌕ Search

Biomedical subjects

Noriko Mutsuga

Publications and source records attributed to Noriko Mutsuga.

10 recordsLinked to original sources
PubMed2006

FGF2 posttranscriptionally down-regulates expression of SDF1 in bone marrow stromal cells through FGFR1 IIIc.

The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively expressed by bone marrow stromal cells and plays key roles in hematopoiesis. Fibroblast growth factor 2 (FGF2), a member of the FGF family that plays important roles in developmental morphogenic processes, is abnormally elevated in the bone marrow from patients with clonal myeloid disorders and other disorders where normal hematopoiesis is impaired. Here, we report that FGF2 reduces SDF-1 secretion and protein content in bone marrow stromal cells. By inhibiting SDF-1 production, FGF2 compromises stromal cell support of hematopoietic progenitor cells. Reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFRs) among the 7 known FGFR subtypes. Blocking experiments identified FGFR1 IIIc as the receptor mediating FGF2 inhibition of SDF-1 expression in bone marrow stromal cells. Analysis of the mechanisms underlying FGF2 inhibition of SDF-1 production in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by posttranscriptionally accelerating SDF-1 mRNA decay. Thus, we identify FGF2 as an inhibitor of SDF-1 production in bone marrow stromal cells and a regulator of stromal cell supportive functions for hematopoietic progenitor cells.

Animals↗
PubMed2006

Microarray analysis of gene expression in the supraoptic nucleus of normoosmotic and hypoosmotic rats.

1. Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin (OT) gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the OT and VP magnocellular neurons (MCNs) of the hypothalamo-neurohypophysial system (HNS), in order to detect novel genes in this system that might be involved in osmoregulation in the MCNs. 2. For this purpose, we used Affymetrix oligonucleotide arrays to analyze the expression of specific genes in laser microdissected rat SONs, and their changes in expression during chronic hypoosmolality. We identified over 40 genes that had three-fold or more greater expression in the SON versus total hypothalamus, and that also changed more than two fold in expression as a result of the chronic hypoosmolar treatment. These genes contained both novel as well as genes previously known to be present in the SON. All of the raw data for the genes that are expressed in the SON and altered by hypoosmolality can be found on the following NINDS website URL address: http://data.ninds.nih.gov/Gainer/Publications.

Animals↗
PubMed2006

Molecular analysis of the magnocellular neuroendocrine phenotype: from the micropunch to laser microdissection.

Microdissection of selected regions of central nervous system (CNS) has provided the basis of modern chemoarchitectonics. Laser microdissection is a modern variant of the "Palkovits punch" technique and used together with gene array analysis has revolutionalized CNS molecular analysis. Here we describe the use of such an approach to elucidate molecules selectively expressed in magnocellular neuroendocrine cells (MCNs) in the supraoptic nucleus (SON). We found 123 genes that are preferentially expressed in the SON, and of these, 89 were substantially osmoregulated in their expression. One of these, C1q domain containing 1, is a novel gene that is osmoregulated much more than even vasopressin itself.

Animals↗
PubMed2005

Studies of oxytocin and vasopressin gene expression in the rat hypothalamus using exon- and intron-specific probes.

To develop a comprehensive approach for the study of oxytocin (OT) and vasopressin (VP) gene expression in the rat hypothalamus, we first developed an intronic riboprobe to measure OT heteronuclear RNA (hnRNA) levels by in situ hybridization histochemistry (ISHH). Using this 84-bp riboprobe, directed against intron 2 of the OT gene, we demonstrate strong and specific signals in neurons confined to the supraoptic (SON) and paraventricular (PVN) nuclei of the rat hypothalamus. We used this new intronic OT probe, together with other well-established intronic and exonic OT and VP probes, to reevaluate OT and VP gene expression in the hypothalamus under two classical physiological conditions, acute osmotic stimulation, and lactation. We found that magnocellular neurons in 7- to 8-day lactating female rats exhibit increased OT but not VP hnRNA. Since VP mRNA is increased during lactation, this suggests that decreased VP mRNA degradation during lactation may be responsible for this change. In contrast, whereas there was the expected large increase in VP hnRNA after acute salt loading, there was no change in OT hnRNA, suggesting that acute hyperosmotic stimuli produce increased VP but not OT gene transcription. Hence, the use of both exon- and intron-specific probes, which distinguish the changes in hnRNA and mRNA levels, respectively, can provide insight into the relative roles of transcription and mRNA degradation processes in changes in gene expression evoked by physiological stimuli.

Animals↗
PubMed2005

Prostaglandin E2 promotes degranulation-independent release of MCP-1 from mast cells.

Mast cells (MCs) are common components of inflammatory infiltrates and a source of proangiogenic factors. Inflammation is often accompanied by vascular changes. However, little is known about modulation of MC-derived proangiogenic factors during inflammation. In this study, we evaluated the effects of the proinflammatory mediator prostaglandin E2 (PGE2) on MC expression and release of proangiogenic factors. We report that PGE2 dose-dependently induces primary MCs to release the proangiogenic chemokine monocyte chemoattractant protein-1 (MCP-1). This release of MCP-1 is complete by 2 h after PGE2 exposure, reaches levels of MCP-1 at least 15-fold higher than background, and is not accompanied by degranulation or increased MCP-1 gene expression. By immunoelectron microscopy, MCP-1 is detected within MCs at a cytoplasmic location distinct from the secretory granules. Dexamethasone and cyclosporine A inhibit PGE2-induced MCP-1 secretion by approximately 60%. Agonists of PGE2 receptor subtypes revealed that the EP1 and EP3 receptors can independently mediate MCP-1 release from MCs. These observations identify PGE2-induced MCP-1 release from MCs as a pathway underlying inflammation-associated angiogenesis and extend current understanding of the activities of PGE2.

Angiogenesis Inducing Agents↗
PubMed2005

APeg3, a novel paternally expressed gene 3 antisense RNA transcript specifically expressed in vasopressinergic magnocellular neurons in the rat supraoptic nucleus.

Vasopressin (VP) and oxytocin (OT) play critical roles in the regulation of salt and water balance, lactation, and various behaviors and are expressed at very high levels in specific magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system (HNS). In addition to the cell-specific expression of the VP and OT genes in these cells, there are other transcripts that are preferentially expressed in the VP or OT MCNs. One such gene, paternally expressed gene 3 (Peg3), is an imprinted gene expressed exclusively from the paternal allele that encodes a Kruppel-type zinc finger-containing protein involved in maternal behavior and is abundantly expressed in the VP-MCNs. We report here the robust expression in the VP-MCNs of an RNA, which we designate APeg3 that is transcribed in the antisense direction to the 3' untranslated region of the Peg3 gene. The APeg3 mRNA is about 1 kb in size, and the full-length sequence of APeg3, as determined by 5' and 3' RACE, contains an open reading frame that predicts a protein of 93 amino acids and is predominantly expressed in VP-MCNs. Both Peg3 and APeg3 gene expression in the VP-MCNs increase during systemic hyperosmolality in vivo, demonstrating that both of these genes are osmoregulated.

3' Untranslated Regions↗
PubMed2004

Regulation of gene expression in magnocellular neurons in rat supraoptic nucleus during sustained hypoosmolality.

Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the oxytocin and VP magnocellular neurons of the hypothalamo-neurohypophysial system, to identify genes associated with the magnocellular neuron's adaptation to this physiological condition. Using laser microdissection of the SON, T7-based linear amplification of its RNA, and a 35,319-element cDNA microarray, we compare gene expression profiles between SONs in normoosmolar (control), 1-desamino-[8-D-arginine]-VP-treated normoosmolar, and hypoosmolar rats. We found 4959 genes with statistically significant differences in expression between normosmolar control and the hypoosmolar SONs, with 1564 of these differing in expression by more than 2-fold. These genes serve a wide variety of functions, and most were up-regulated in gene expression in hypoosmolar compared with control SONs. Of these, 90 were preferentially expressed in the SON, and 44 coded for transcription-related factors, of which 15 genes were down-regulated and 29 genes were up-regulated in the hypoosmolar rat SONs. None of these transcription-related factor genes significantly changed in expression after sustained 1-desamino-[8-D-arginine]-VP-treatment alone, indicating that these changes were associated with the hypoosmolar state and not due solely to a decreased activity in the SON. Quantitative in situ hybridization histochemistry was selectively used to confirm and extend these microarray observations. These results indicate that the hypoosmolar state is accompanied by a global, but selective, increase in expression of a wide variety of regulatory genes in the SON.

Animals↗
PubMed2004

Selective gene expression in magnocellular neurons in rat supraoptic nucleus.

Oxytocin- and vasopressin-producing magnocellular neurons (MCNs) of the hypothalamo-neurohypophysial system are the only neuronal phenotypes present in the rat supraoptic nucleus (SON). Laser microdissection of the SON, extraction and T7-based amplification of its RNAs, and analysis of the resulting cDNAs by hybridization on a 35, 319 element DNA microarray have provided a detailed composite view of the gene expression profile of the MCNs. The genes expressed in the SON were compared with those expressed in a reference tissue consisting of total hypothalamus, and this "expression ratio" indicated which genes were preferentially expressed in the SON. Of the 26,000 unique genes on the array, 1385 were found to be expressed in the SON at levels more than two times greater than in the hypothalamus as a whole. Of these, 123 were expressed > or =3.4-fold higher in the SON versus hypothalamus. Most of these preferentially expressed genes were not previously known to be expressed in the MCNs. Quantitative and double-label in situ hybridization histochemistry was used selectively to confirm a number of these microarray observations and to evaluate the osmotic regulation and cell-specific expression of these genes, respectively.

Animals↗
PubMed2003

Sodium bicarbonate infusion test: a new method for evaluating parathyroid function.

We have developed a new test for estimating the secretory capacity of parathyroid hormone (PTH) from the parathyroid gland. Sodium bicarbonate solution [8.4% (w/v); 35 ml/m(2) body surface area] was infused for 2 min, and blood samples for the determination of plasma ionized calcium, plasma PTH (intact, midregion, carboxy-terminus) and related parameters were serially obtained. In 8 healthy volunteers, the mean (+/-SE) plasma ionized calcium fell promptly and significantly (from 1.21 +/- 0.01 to 1.11 +/- 0.01 mmol/L) after the sodium bicarbonate infusion. The mean (+/-SE) plasma intact PTH increased promptly and significantly, by more than four fold (42.3 +/- 4.2 to 182.4 +/- 34.7 pg/ml), and then gradually returned to basal levels. In patients with partial hypoparathyroidism who have detectable basal plasma levels of PTH, the absolute increment in PTH levels was much less, and in the plasma obtained from patients with complete hypoparathyroidism, absolutely no response was observed. Plasma obtained from patients diagnosed with primary hyperparathyroidism (parathyroid adenoma or hyperplasia) has high basal PTH levels. The response to the sodium bicarbonate infusion in these patients was markedly blunted (less than a two-fold increase in all cases examined). No significant adverse effects were observed during the procedure. Therefore, the sodium bicarbonate infusion test is a simple and sensitive method to stimulate PTH release, and is clinically useful for evaluating parathyroid gland function.

Adult↗