Alteration in Uterine Protease-Activated Receptor 2 Expression in Preterm Birth Induced Experimentally inBrp-39Null Mutant Mice

2018 ◽  
Vol 26 (6) ◽  
pp. 713-723
Author(s):  
Ja Yun Jang ◽  
Yi Seul Kim ◽  
Yu Mi Han ◽  
So Young Kang ◽  
Jung-Sun Kim
Keyword(s):  
Preterm Birth ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Glycosyl Hydrolase ◽  
Placental Tissue ◽  
Altered Expression ◽  
Protein Expressions ◽  
Before And After ◽  
Associated Proteins ◽  
Protease Activated Receptor 2

Breast regression protein 39 (Brp-39) is a mouse homolog of human Chitinase 3-like 1, which belongs to the 18-glycosyl-hydrolase family and plays a role in inflammatory reaction and tissue remodeling. The aim of this study is to investigate the role of Brp-39 in a mouse model of preterm birth. Pregnant wild-type (WT) or Brp-39(−/−) mice were injected intraperitoneally with lipopolysaccharide (LPS) at embryonic day 15. Pregnancy outcomes were evaluated for 24 hours after LPS injection. Quantitative real-time polymerase chain reaction and immunoblotting were performed to analyze messenger RNA (mRNA) and protein expressions of cytokines and contraction-associated proteins in uterine and/or placental tissue after LPS injection. LPS injection led to preterm birth in both WT and Brp-39(−/−) mice, but the proportion of pubs delivered was reduced in Brp-39(−/−) mice, along with a longer interval from the LPS injection to delivery, compared to WT mice. Inflammatory cell infiltration and mRNA expression of cytokines and Ptgs2 in the uteri and the placentas were not significantly different between WT and Brp-39(−/−) mice. Par-2 mRNA expression in the WT uteri was increased before delivery after LPS injection and decreased after delivery, while there was no significant change in Par-2 expression in the Brp-39(−/−) uteri. Protein expressions of Par-2 and Ptgs2 were lower in the Brp-39(−/−) uteri than in the WT uteri before and after delivery. Attenuated preterm birth in Brp-39(−/−) mice indicates the significance of Brp-39 during murine preterm birth. Altered expression of Par-2 in Brp-39(−/−) uteri suggests its potential role in attenuated preterm birth of Brp-39(−/−) mice.

Fetal Membrane Inflammation Induces Preterm Birth Via Toll-Like Receptor 2 in Mice With Chronic Gingivitis

2018 ◽  
Vol 26 (7) ◽  
pp. 869-878 ◽  
Author(s):  
Haruhisa Konishi ◽  
Satoshi Urabe ◽  
Hiroshi Miyoshi ◽  
Yuko Teraoka ◽  
Tomoko Maki ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Real Time ◽  
Messenger Rna ◽  
Contractile Activity ◽  
Fetal Membrane ◽  
Toll Like Receptor ◽  
Uterine Contractility ◽  
Associated Proteins ◽  
Toll Like Receptor 2 ◽  
Cox 2

Inflammation is associated with preterm birth. We previously described a mouse model of chronic inflammation-induced preterm birth after dental Porphyromonas gingivalis infection. The aim of this study was to employ this model system to investigate the mechanisms through which enhanced uterine contractility induces preterm birth. Messenger RNA (mRNA) encoding contraction-associated proteins, such as oxytocin receptors, was measured at various gestational time points by real-time polymerase chain reaction (PCR). Spontaneous and oxytocin-induced uterine contractile activity at gestational day 18 was assessed using a tissue organ bath. The expression levels of Toll-like receptor 2 (TLR2), TLR4, cyclooxygenase (COX)-2, nuclear factor-kappa B (NF-κB) p65, and p38 mitogen-activated protein kinase (MAPK) on gestational day 18 were also determined by real-time PCR or Western blotting. Messenger RNA encoding contraction-associated proteins was increased at gestational day 18, and the spontaneous contractile activity (1.6-fold greater area under the contraction curve) and sensitivity to oxytocin (EC50: 8.8 nM vs 2.2 nM) were enhanced in the P gingivalis group compared to those in the control group. In the P gingivalis group, COX-2 mRNA expression was not elevated in the placenta or myometrium but was upregulated 2.3-fold in the fetal membrane. The TLR2 mRNA levels in the fetal membrane were 2.7-fold higher in the P gingivalis group, whereas TLR4 levels were not elevated. Activation of the NF-κB p65 and p38 MAPK pathways was enhanced in the fetal membrane of the P gingivalis group. Thus, in mice with chronic dental P gingivalis infection, TLR2-induced inflammation in the fetal membrane leads to upregulation of uterine contractility, leading to preterm birth.

Altered Expression of MLH1, MSH2, and MSH6 in Predisposition to Hereditary Nonpolyposis Colorectal Cancer

2003 ◽  
Vol 21 (19) ◽  
pp. 3629-3637 ◽  
Author(s):  
Elise Renkonen ◽  
Yange Zhang ◽  
Hannes Lohi ◽  
Reijo Salovaara ◽  
Wael M. Abdel-Rahman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Population Based ◽  
Altered Expression ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Hereditary Nonpolyposis

Purpose: A considerable fraction (30% to 70%) of families with verified or putative hereditary nonpolyposis colorectal cancer fails to show mutations in DNA mismatch repair (MMR) genes. Our purpose was to address the genetic etiology of such families. Materials and Methods: We scrutinized a population-based cohort of 26 families from Finland that had screened mutation-negative by previous techniques. Blood was tested for allelic messenger RNA (mRNA) expression of MLH1, MSH2, and MSH6 by single nucleotide primer extension (SNuPE), and tumor tissue for MMR protein expression by immunohistochemistry (IHC) as well as for microsatellite instability (MSI). Full-length cDNAs of genes implicated by SNuPE or IHC were cloned and sequenced. Results: Unbalanced mRNA expression of MLH1 alleles was evident in two families. An inherited nonsense mutation was subsequently identified in one family, and complete silencing of the mutated allele was identified in the other family. Extinct protein expression by IHC implicated MLH1 in these two and in four other families, MSH2 in four families, and MSH6 in one family. Although no unequivocal genomic mutations were detected in the latter families, haplotype and other findings provided support for heritable defects. With one exception, all tumors with IHC alterations showed MSI, in contrast to the remaining families, which showed neither IHC changes nor MSI. Conclusion: Our expression-based strategy stratified the present “mutation-negative” cohort into two discrete categories: families linked to the major MMR genes MLH1, MSH2, and MSH6 (11 [42%] of 26) and those likely to be associated with other, as yet unknown susceptibility genes (15 [58%] of 26).

scholarly journals Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women

2017 ◽  
Vol 102 (12) ◽  
pp. 4588-4595 ◽  
Author(s):  
Natalia Hetemäki ◽  
Hanna Savolainen-Peltonen ◽  
Matti J Tikkanen ◽  
Feng Wang ◽  
Hanna Paatela ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Messenger Rna ◽  
Metabolic Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Subcutaneous Fat ◽  
Estrogen Metabolism ◽  
Serum Samples ◽  
Estrogen Exposure

Abstract Context In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. Objective We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. Design, Setting, Patients, and Interventions AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Results Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Conclusions Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

Thrombosis and Altered expression of Intercellular Adhesion Molecule-1 (Icam-1) after Avulsion Injury in Rat Vessels

2004 ◽  
Vol 29 (3) ◽  
pp. 228-232 ◽  
Author(s):  
N. ISOGAI ◽  
H. TANAKA ◽  
S. ASAMURA
Keyword(s):  
Mrna Expression ◽  
Adhesion Molecule ◽  
Microscopic Analysis ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Post Injury ◽  
Electron Microscopic ◽  
Altered Expression ◽  
Avulsion Injury

This study was undertaken to characterize the relative degrees of arterial and venous trauma after graded avulsion injuries. Rat femoral arteries and veins were subjected to reproducible avulsion injuries using forces of between 60 and 220 g. Thrombotic occlusion occurred at lower avulsion forces in veins than in arteries. Histologic and scanning electron microscopic analysis indicated increased endothelial disruption and exposed elastic lamina with increasing avulsion force in both vessels, but more prominently in arteries. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression was evident at 3 and 6 hours after avulsion injury in veins, but only with higher avulsion force injuries in arteries. ICAM-1 mRNA expression was not found in either vessel before or after this 3 to 6 hour post-injury interval. These results indicate that the amount of avulsion force to which traumatized extremity vessels are subjected has a direct effect on the degree of intimal injury and subsequent thrombosis.

Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb

2015 ◽  
Vol 6 (6) ◽  
pp. 558-572 ◽  
Author(s):  
D. J. Carr ◽  
J. S. Milne ◽  
R. P. Aitken ◽  
C. L. Adam ◽  
J. M. Wallace
Keyword(s):  
Dna Methylation ◽  
Growth Hormone ◽  
Sexual Dimorphism ◽  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Messenger Rna ◽  
Methylation Status ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Increased Risk

Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ∼50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (M<F, P=0.008). IGF1 mRNA:18S and plasma IGF1 were M>F (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=−0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002–0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.

Lower antioxidant capacity in the prefrontal cortex of individuals with schizophrenia

2017 ◽  
Vol 52 (7) ◽  
pp. 690-698 ◽  
Author(s):  
Yiru Zhang ◽  
Vibeke Sørensen Catts ◽  
Cynthia Shannon Weickert
Keyword(s):  
Prefrontal Cortex ◽  
Antioxidant Capacity ◽  
Mrna Expression ◽  
Antioxidant System ◽  
Messenger Rna ◽  
Total Glutathione ◽  
Protein Levels ◽  
Significant Difference ◽  
Dorsolateral Prefrontal ◽  
And Control

Objective: The glutathione (GSH) pathway is the main antioxidant system to protect against oxidative stress in the human brain. In this study, we tested whether molecular components of the GSH antioxidant system are changed in dorsolateral prefrontal cortex tissue from people with schizophrenia compared to controls. Method: The levels of total glutathione and reduced GSH were determined by fluorometric assay via quantifying thiols in extracts from frontal cortex of 68 people. Immunoblotting was used to measure levels of enzymes responsible for maintaining GSH, the glutamyl-cysteine ligase (GCL) catalytic subunit (GCLC) and the GSH peroxidase (GPx)-like protein ( n = 74). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure GCLC messenger RNA (mRNA) expression. Results: Both total glutathione ( t(66) = 2.467, p = 0.016) and reduced GSH ( t(66) = 3.001, p = 0.004) levels were significantly less in people with schizophrenia than in controls. However, there were no significant differences in either GCLC-like protein ( t(72) = −1.077, p = 0.285) or GCLC mRNA expression ( t(71) = −0.376, p = 0.708) between people with schizophrenia and control subjects. There was also no significant difference of GPx-like protein levels between schizophrenia and controls ( t(72) = −0.060, p = 0.952). Moreover, no significant correlations of putative confounding factors with GSH changes were detected. Discussion: These results suggest that people with schizophrenia have impaired GSH antioxidant capacity, alongside normal levels of key regulatory proteins.

Tissue Factor Expression in Vital Organs during Murine Traumatic Shock 

1999 ◽  
Vol 91 (6) ◽  
pp. 1844-1844 ◽  
Author(s):  
Valerie E. Armstead ◽  
Irina L. Opentanova ◽  
Alexander G. Minchenko ◽  
Allan M. Lefer
Keyword(s):  
Small Intestine ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Messenger Rna ◽  
Mrna Level ◽  
Regulatory Elements ◽  
Traumatic Shock ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Nf Kappab

Background Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the extrinsic pathway of coagulation that has been shown to have a role in the pathophysiology of sepsis and reperfusion injury. The purpose of this study was to investigate TF expression in vital organs and to determine possible regulatory mechanisms of TF expression in the lung during traumatic shock in rats. Methods Noble-Collip drum trauma was induced in anesthetized Sprague-Dawley rats. Anesthetized rats without trauma served as controls. TF activity was measured in plasma and lung tissue. TF messenger RNA (mRNA) was measured in the lung, liver, and small intestine using ribonuclease protection assays. Electromobility shift assays were used to quantify binding of nuclear extracts from lung to TF-specific consensus domains for transcription factors NF-kappaB and AP-1. Results TF activity in plasma increased up to 14-fold and +232% in the lung (P &lt; 0.001 for plasma and lung) 2 h after trauma. TF mRNA level was significantly increased in the lungs (P &lt; 0.01), small intestine (P &lt; 0.01), and liver (P &lt; 0.05) 1 h after trauma compared to sham-operated control rats. TF mRNA expression continued to increase in the lungs and the liver (both, P &lt; 0.001) 2 h after trauma TF sequence-specific complex binding to AP-1 and NF-kappaB domains was enhanced in the lungs of trauma rats (+395%, P &lt; 0.001 and +168%, P &lt; 0.001, respectively). Conclusions These results suggest that TF may play an important role in the pathophysiology of severe trauma and that regulatory elements AP-1 and NF-kappaB may be involved in the regulation of TF mRNA expression in traumatic shock.

Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscle

2005 ◽  
Vol 25 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Anita S. Mannikarottu ◽  
Michael E. DiSanto ◽  
Stephen A. Zderic ◽  
Alan J. Wein ◽  
Samuel Chacko
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Thin Filament ◽  
Bladder Smooth Muscle ◽  
Altered Expression ◽  
Associated Proteins ◽  
Urinary Bladder Smooth Muscle
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