mRNA Changes (mrna + change)

Distribution by Scientific Domains


Selected Abstracts


Ex vivo TCR-induced leukocyte gene expression of inflammatory mediators is increased in type 1 diabetic patients but not in overweight children

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2010
Jaime S. Rosa
Abstract Background Abnormal systemic concentrations of proinflammatory cytokines/chemokines have been implicated in the development of long-term cardiovascular complications in type 1 diabetes (T1DM) and obesity. Whether leukocyte white blood cell (WBC) gene expression of these proinflammatory mediators contributes to their increased systemic levels, however, remains unclear, especially in the pediatric patient populations. This study examines mRNA changes of 9 cytokines and chemokines in WBCs following ex vivo immunostimulation from 9 T1DM (13.4 ± 0.5 year, 4F/5 M), 23 overweight (OW, 12.3 ± 0.5 year, 10F/13M, BMI% 97.1 ± 0.5 and > 90.0), and 21 healthy (CL, 13.8 ± 0.7 year, 9F/12 M, BMI% 59.6 ± 4.6 and < 85.0) children. Methods All subjects had been maintained in euglycemic conditions for at least 90 min before blood draws. Whole blood was then sampled and incubated with anti-T-cell receptor (TCR) antibody or heat-aggregated IgG (HAG) to stimulate T-cell and Fc receptors (FcR), respectively. After lysis of leukocytes, mRNA levels of six tumor necrosis factor superfamily cytokines (TNFSF2, 5, 6, 7, 9, 14) and three chemokines (CCL8, 20, and CXCL10) were measured using RT-PCR. Results Following TCR stimulation, T1DM displayed significantly greater mRNA responses than CL for TNFSF5, 7, 9, and CCL8, and CXCL10; TNFSF9, CCL8, and CXCL10 were also significantly higher in T1DM than OW; no difference was observed between OW and CL. FcR stimulation induced similar responses across groups. Conclusions Leukocytes of T1DM children displayed exaggerated gene expression in response to ex vivo TCR induction of five key proinflammatory cytokines/chemokines. This elevated leukocyte gene expression may be one of the pathophysiological contributors to the development of vascular complications in T1DM. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Leptin and endothelin-1 mediated increased extracellular matrix protein production and cardiomyocyte hypertrophy in diabetic heart disease

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2009
Pijush Majumdar
Abstract Background We investigated the role of leptin and its interaction with endothelin 1 (ET-1) in fibronectin (FN) synthesis and cardiomyocyte hypertrophy, two characteristic features of diabetic cardiomyopathy. Methods Endothelial cells [human umbilical vein endothelial cells (HUVECs)] were examined for FN production and neonatal rat cardiomyocytes for hypertrophy, following incubation with glucose, ET-1, leptin and specific blockers. FN, ET-1, leptin and leptin receptors mRNA expression and FN protein were measured. Myocytes were also morphometrically examined. Furthermore, hearts from streptozotocin-diabetic rats were analysed. Results Glucose caused increased FN mRNA and protein expression in HUVECs and cardiomyocytes hypertrophy along with upregulation of ET-1 mRNA, leptin mRNA and protein. Glucosemimetic effects were seen with leptin and ET-1. Leptin receptor antagonist (leptin quadruple mutant) and dual endothelin A endothelin B (ETA/ETB) receptor blocker bosentan normalized such abnormalities. Hearts from the diabetic animals showed hypertrophy and similar mRNA changes. Conclusion These data indicate that in diabetes increased FN production and cardiomyocyte hypertrophy may be mediated through leptin with its interaction with ET-1. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Evidence for Increased Neuropeptide Y Synthesis in Mediobasal Hypothalamus in Relation to Parental Hyperphagia and Gonadal Activation in Breeding Ring Doves

JOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2007
S. Ramakrishnan
Like lactating mammals, male and female ring dove parents increase their food consumption to meet the energetic challenges of provisioning their young. To clarify the neurochemical mechanisms involved, the present study investigated the relationship between parental hyperphagia and changes in activity of the potent orexigen neuropeptide Y (NPY) in the hypothalamus of breeding doves. Changes in NPY-immunoreactive (NPY-ir) cell numbers in the tuberal hypothalamus of male and female doves were examined by immunocytochemistry at six stages of the breeding cycle. Parallel NPY mRNA measurements were recorded in mediobasal hypothalamus (which includes the tuberal hypothalamus) by semiquantitative reverse transcription-polymerase chain reaction using 18S rRNA as the internal standard. NPY mRNA changes were also measured in the mediobasal hypothalamus of nonbreeding doves following intracranial administration of prolactin, an orexigenic hormone that is elevated in the plasma of parent doves, and in response to food deprivation, which mimics the negative energy state that develops in parents as they provision their growing young. NPY-ir cell numbers in the tuberal hypothalamus and NPY mRNA levels in the mediobasal hypothalamus were significantly higher in breeding males and females during the period of parental hyperphagia after hatching than during the late incubation period when food intake remains unchanged. In nonbreeding doves, food deprivation and prolactin treatment increased NPY mRNA in this region by two- to three-fold, which suggests that NPY expression is sensitive to hormonal and metabolic signals associated with parenting. We conclude that NPY synthesis is increased in the mediobasal hypothalamus during the posthatching period, which presumably supports increased NPY release and resulting parental hyperphagia. NPY-ir and mRNA were also high in the mediobasal hypothalamus prior to egg laying when food intake remained unchanged. Several lines of evidence suggest that this elevation in NPY supports the increased gonadal activity that accompanies intense courtship and nest building interactions in breeding doves. [source]


p38 MAPK inhibition modulates rabbit nucleus pulposus cell response to IL-1,

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2008
Rebecca K. Studer
Abstract Analysis of disc gene expression implicated IL-1 in the development of intervertebral disc degeneration (IDD) in a rabbit stab model. The purpose of these studies is to determine the role of p38 Mitogen Activated Protein Kinase (p38 MAPK) signaling in nucleus pulposus cell response to IL-1, and to compare rabbit nucleus pulposus (rNP) cell responses to IL-1 activation with those in a stab model of disc degeneration. NP cells maintained in alginate bead culture were exposed to IL-1, with or without p38 MAPK inhibition. RNA was isolated for reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression, conditioned media analyzed for accumulation of nitric oxide (NO) and prostaglandin E-2 (PGE-2), and proteoglycan synthesis measured after 10 days. IL-1 upregulation of mRNA for cycloxygenase-2 (COX-2), matrix metalloproteinase-3 (MMP-3), IL-1, and IL-6, was blunted by p38 inhibition while downregulation of matrix proteins (collagen I, collagen II, aggrecan) and insulin-like-growth-factor I (IFG-1) was also reversed. mRNA for tissue inhibitor of matrixmetalloproteinase-1 (TIMP-1) was modestly increased by IL-1, while those for Transforming Growth Factor-, (TGF-,) SOX-9, and versican remained unchanged. Blocking p38 MAPK reduced IL-1 induced NO and PGE-2 accumulation and partially restored proteoglycan synthesis. p38 MAPK inhibition in control cells increased mRNA for matrix proteins (aggrecan, collagen II, versican, collagen I) and anabolic factors (IGF-1, TGF, and SOX-9) from 50% to 120%, decreased basal PGE-2 accumulation, but had no effect on message for TIMP-1, MMP-3, or COX-2. Inhibition of p38 MAPK in cytokine-activated disc cells blunts gene expression and production of factors associated with inflammation, pain, and disc matrix catabolism while reversing IL-1 downregulation of matrix protein gene expression and proteoglycan synthesis. The results support the hypothesis that IL-1 could be responsible for many of the mRNA changes seen in rabbit NP in the stab model of disc degeneration, and uphold the concept that development of molecular techniques to block p38 MAPK could provide a therapeutic approach to slow the course of intervertebral disc degeneration. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:991,998, 2008 [source]