Placental expression of proteases and their inhibitors in patients with HELLP syndrome

2009 ◽  
Vol 390 (11) ◽  
Author(s):  
Stephanie Pildner von Steinburg ◽  
Achim Krüger ◽  
Thorsten Fischer ◽  
Karl-Theodor Mario Schneider ◽  
Manfred Schmitt
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Plasminogen Activator ◽  
Hellp Syndrome ◽  
Mrna Level ◽  
Placental Tissue ◽  
Northern Blotting ◽  
Trophoblast Invasion ◽  
Matrix Remodeling ◽  
Elevated Liver Enzymes

AbstractIn preeclampsia and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, impaired trophoblast invasion and excessive fibrin deposition in the placental intervillous space is associated with fetal compromise. However, little information is available whether modulation of placental protease expression – potentially causing impaired trophoblast invasion – is associated with the HELLP syndrome. Total RNA and protein were extracted from placental tissue from 11 females with HELLP syndrome and 8 controls matched for gestational age. mRNA expression of matrix metalloprotease (MMP) -2 and -9, tissue inhibitors of metalloprotease (TIMP) -1, -2, and -3, and urokinase-type plasminogen activator receptor (uPAR) was determined by Northern blotting. Protein expression of MMP-2 and -9, and TIMP-1 and -2 was detected by Western blotting and that of uPA, uPAR, and plasminogen activator inhibitor (PAI) -1 by ELISA. In patients with HELLP syndrome, mRNA expression of MMP-2 and TIMP-2 was decreased, whereas TIMP-1 and -3 levels were unchanged. MMP-9 and uPAR mRNA was undetectable in both groups. Protein expression of all investigated proteolytic factors remained unchanged. Our findings at the mRNA level suggest a decrease in matrix remodeling in placentae from patients with HELLP syndrome compared with control pregnancies, although this is not supported at the protein level.

scholarly journals Altered placental expression of kisspeptin and its receptor in pre-eclampsia

2012 ◽  
Vol 214 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Judith E Cartwright ◽  
Paula Juliet Williams
Keyword(s):  
Mrna Expression ◽  
Cancer Metastasis ◽  
Placental Tissue ◽  
Normal Pregnancy ◽  
Trophoblast Invasion ◽  
Term Pregnancy ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Normal Term ◽  
In Pregnancy

Kisspeptin, originally identified as metastatin, important in preventing cancer metastasis, has more recently been shown to be important in pregnancy. Roles indicated for kisspeptin in pregnancy include regulating trophoblast invasion and migration during placentation. The pregnancy-specific disorder pre-eclampsia (PE) is now accepted to begin with inadequate trophoblast invasion and the current study therefore sets out to characterise placental expression of both kisspeptin (KISS1) and its receptor (KISS1R) throughout pregnancy and in PE. Placental tissue was obtained from women undergoing elective surgical termination of early pregnancy (n=10) and from women following Caesarean section at term in normal pregnancy (n=10) and with PE (n=10). Immunohistochemistry of paraffin embedded sections and western immunoblotting were performed to assess protein localisation and expression. Quantitative real-time PCR was carried out to evaluate mRNA expression of both KISS1 and KISS1R. Protein and mRNA expression was found to mirror each other with KISS1 expression found to be reduced in PE compared with that in normal term pregnancy. Interestingly, KISS1R expression at both the mRNA and protein levels was found to be increased in PE compared with that in normal term pregnancy. The current findings of increased KISS1R expression may represent a mechanism by which functional activity of KISS1 is higher in PE than in normal pregnancy. Higher levels of activity of KISS1R may be involved in inhibition of trophoblast invasion and angiogenesis, which are associated with PE.

Wnt/β-Catenin and Hippo Pathway Deregulation in Mammary Tumors of Humans, Dogs, and Cats

2020 ◽  
Vol 57 (6) ◽  
pp. 774-790
Author(s):  
Alessandro Sammarco ◽  
Chiara Gomiero ◽  
Roberta Sacchetto ◽  
Giorgia Beffagna ◽  
Silvia Michieletto ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Level ◽  
Hippo Pathway ◽  
Mammary Tumors ◽  
Breast Cancers ◽  
Tumor Tissues ◽  
Mrna And Protein Expression ◽  
Polymerase Chain

Mammary cancer is a common neoplasm in women, dogs, and cats that still represents a therapeutic challenge. Wnt/β-catenin and Hippo pathways are involved in tumor progression, cell differentiation, and metastasis. The aim of this study was to evaluate mRNA and protein expression of molecules involved in these pathways in human (HBC), canine (CMT), and feline mammary tumors (FMT). Real-time quantitative polymerase chain reaction (qPCR) for β-catenin, CCND1, YAP, TAZ, CTGF, and ANKRD1, western blotting for YAP, TAZ, and β-catenin, and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), ERBB2, β-catenin, and YAP/TAZ were performed on mammary tumor tissues. The protein expression of active β-catenin was higher in tumors than in healthy tissues in all 3 species. The mRNA expression of the downstream gene CCND1 was increased in HBC ER+ and CMTs compared to healthy tissues. Membranous and cytoplasmic protein expression of β-catenin were strongly negatively correlated in all 3 species. Tumors showed an increased protein expression of YAP/TAZ when compared to healthy tissues. Notably, YAP/TAZ expression was higher in triple negative breast cancers when compared to HBC ER+ and in FMTs when compared to CMTs. The mRNA expression of β-catenin, YAP, TAZ, CTGF, and ANKRD1 was not different between tumors and healthy mammary gland in the 3 species. This study demonstrates deregulation of Wnt/β-catenin and Hippo pathways in mammary tumors, which was more evident at the protein rather than the mRNA level. Wnt/β-catenin and Hippo pathways seem to be involved in mammary carcinogenesis and therefore represent interesting therapeutic targets that should be further investigated.

Silencing non-SMC chromosome-associated polypeptide G inhibits proliferation and induces apoptosis in hepatocellular carcinoma cells

2018 ◽  
Vol 96 (12) ◽  
pp. 1246-1254 ◽  
Author(s):  
Kaikun Liu ◽  
Yumin Li ◽  
Bo Yu ◽  
Furong Wang ◽  
Taiyu Mi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Mrna Level ◽  
A Subunit ◽  
Underlying Mechanisms ◽  
Colony Forming Capacity ◽  
Hcc Cells

The present study was designed to investigate the significance of non–structural maintenance of chromosomes (non-SMC) chromosome-associated polypeptide G (NCAPG), a subunit of condensin complex I, in the development of hepatocellular carcinoma (HCC). NCAPG protein expression in human HCC and paracancerous hepatic tissues were examined using immunohistochemistry, and NCAPG mRNA expression in HCC cell lines were quantified using quantitative RT–PCR. Lentivirus-mediated RNA interference was used to silence NCAPG in HCC cells. Cell proliferation was monitored by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Apoptosis was determined by flow cytometry. The results showed that increased protein expression of NCAPG was found in HCC tissues compared with the matched paracancerous hepatic tissues. At the mRNA level, increased expression of NCAPG was found in HCC cells as opposed to the normal hepatocytes. Silencing of NCAPG in BEL-7404 and SMMC-7721 cells led to decreased cell proliferation and increased apoptosis. These changes were associated with increased mRNA expressions of P53, P27, and Bad, but decreased mRNA expression of EGFR, Akt, survivin, and JNK. NCAPG might play an oncogenic role in the development of liver cancer. Further studies to clarify its role and underlying mechanisms in the development of liver cancer are warranted.

scholarly journals Thyroid Hormone Increases mRNA and Protein Expression of Na+-K+-ATPase α2 and β1 Subunits in Human Skeletal Muscles

2007 ◽  
Vol 92 (1) ◽  
pp. 353-358 ◽  
Author(s):  
Bunyong Phakdeekitcharoen ◽  
Suchart Phudhichareonrat ◽  
Chathchai Pookarnjanamorakot ◽  
Chusak Kijkunasathian ◽  
Nattha Tubtong ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Protein Expression ◽  
Mrna Expression ◽  
Skeletal Muscles ◽  
Vastus Lateralis ◽  
Mrna Level ◽  
Before And After ◽  
Hyperthyroid Patients ◽  
Relative Mrna Expression ◽  
Human Skeletal Muscles

Abstract Context: Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent skeletal muscles. No study has examined this relationship in human tissues. Objective: This study investigated the effect of hyperthyroid status on the expression of the α- and β-subunits of the Na+-K+-ATPase. Design: The vastus lateralis muscles from eight hyperthyroid patients were biopsied before and after treatment. Ten age-matched euthyroid subjects served as controls. Results: In hyperthyroid patients, the average T3 level was three times higher in pretreatment compared with posttreatment (262 ± 75 vs. 86 ± 21 ng/dl, P = 0.001). The relative mRNA expression of the α2, but not α1 or α3, subunit was increased approximately 3-fold in pretreatment (2.98 ± 0.52 vs. 0.95 ± 0.40, P < 0.01), whereas that of β1, not β2 or β3, subunit was increased approximately 2.8-fold in pretreatment (2.83 ± 0.38 vs. 1.10 ± 0.27, P < 0.01). The relative mRNA expression of the α2 and β1 subunits was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P = 0.003, respectively). Immunohistochemistry studies revealed an increase in protein abundance of the α2 and β1, but not α1 or β2, subunits in the plasma membrane of muscle fibers of hyperthyroid patients, which decreased after treatment. Conclusions: This provides the first evidence that, in human skeletal muscles, thyroid hormone up-regulates the Na+-K+-ATPase protein expression at least, in part, at mRNA level, and the α2 and β1 subunits play the important role in this regulation.

scholarly journals ROR1 and ROR2 expression in pancreatic cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongli Liu ◽  
George Sharbeen ◽  
Phoebe Phillips ◽  
Amber L. Johns ◽  
Anthony J. Gill ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Wnt Signalling ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Cytoplasmic Staining

Abstract Background The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq.

Expression of an HSP110 Family, Ischemia-Responsive Protein (irp94), in the Rat Brain after Transient Forebrain Ischemia

2000 ◽  
Vol 55 (5-6) ◽  
pp. 449-454 ◽  
Author(s):  
Hyeon-Song Koh ◽  
Il Soo Moon ◽  
Young-Ho Lee ◽  
Minho Shong ◽  
O-Yu Kwon
Keyword(s):  
Mrna Expression ◽  
Molecular Chaperone ◽  
Parietal Lobe ◽  
Mrna Level ◽  
Occipital Lobe ◽  
Northern Blotting ◽  
Forebrain Ischemia ◽  
External Stimulation ◽  
Transient Forebrain Ischemia ◽  
Occipital Lobes

The transcriptional expression of an ischemia responsive protein (irp94) in the hippocampus of rats was analyzed by Northern blotting. A transient forebrain ischemia was induced in the rats by temporary occluding of the bilateral common carotid arteries (CCAs) for various periods, and then reperfusion. Among the frontal, parietal, temporal and occipital lobes, and the cerebellum and hippocampus, the maximum mRNA expression of irp94 was at the occipital lobe, and the minimum was at the parietal lobe following ten min of forebrain ischemia. The irp94 mRNA expression reached a maximum fifteen min after the transient ischemia. From twenty min on after the ischemia its expression decreased. After a ten-min ischemia and the following reperfusion, irp94 mRNA expression gradually increased in the first twelveh, and then decreased. The expression pattern was like that of the endoplasmic reticulum chaperone, Erp72, but not that of the cytosol chaperone, hsp72. In addition, when intracellular ATP was depleted with antimycin A the mRNA level of irp94 increased in a thyrocyte cell culture model. The results suggest that irp94, like a molecular chaperone, may play a role in protecting the cell against external stimulation, especially after a transient forebrain ischemia. Although future studies of irp94 will be required to clarify the interactions with other intracellular factors inducing ischemia or showing molecular chaperone activity, what is offered here is an insight into its functional role as a component of stress response in neurons that should be considered as a new therapeutic approach for the treatment of ischemia.

scholarly journals Altered mRNA and Protein Expression of Monocarboxylate Transporter MCT1 in the Cerebral Cortex and Cerebellum of Prion Protein Knockout Mice

2021 ◽  
Vol 22 (4) ◽  
pp. 1566
Author(s):  
Sanja Ramljak ◽  
Matthias Schmitz ◽  
Cendrine Repond ◽  
Inga Zerr ◽  
Luc Pellerin
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Prion Protein ◽  
Mrna Level ◽  
Brain Regions ◽  
Cellular Prion Protein ◽  
Monocarboxylate Transporter ◽  
Control Group ◽  
Expression Of Genes ◽  
Subunit Expression

The effect of a cellular prion protein (PrPc) deficiency on neuroenergetics was primarily analyzed via surveying the expression of genes specifically involved in lactate/pyruvate metabolism, such as monocarboxylate transporters (MCT1, MCT2, MCT4). The aim of the present study was to elucidate a potential involvement of PrPc in the regulation of energy metabolism in different brain regions. By using quantitative real-time polymerase chain reaction (qRT-PCR), we observed a marked reduction in MCT1 mRNA expression in the cortex of symptomatic Zürich I Prnp−/− mice, as compared to their wild-type (WT) counterparts. MCT1 downregulation in the cortex was accompanied with significantly decreased expression of the MCT1 functional interplayer, the Na+/K+ ATPase α2 subunit. Conversely, the MCT1 mRNA level was significantly raised in the cerebellum of Prnp−/− vs. WT control group, without a substantial change in the Na+/K+ ATPase α2 subunit expression. To validate the observed mRNA findings, we confirmed the observed change in MCT1 mRNA expression level in the cortex at the protein level. MCT4, highly expressed in tissues that rely on glycolysis as an energy source, exhibited a significant reduction in the hippocampus of Prnp−/− vs. WT mice. The present study demonstrates that a lack of PrPc leads to altered MCT1 and MCT4 mRNA/protein expression in different brain regions of Prnp−/− vs. WT mice. Our findings provide evidence that PrPc might affect the monocarboxylate intercellular transport, which needs to be confirmed in further studies.

Early-Onset Preeclampsia with Pulmonary Edema and Massive Ascites: A Rare Presentation of Severe Preeclampsia or Concomitant Diagnoses?

2020 ◽  
Vol 2020 ◽  
Author(s):  
Elizabeth St. Laurent ◽  
Rebecca Fryer-Gordon ◽  
Tom McNeilis, ◽  
Leonard B. Goldstein
Keyword(s):  
Pulmonary Edema ◽  
Early Onset ◽  
Hellp Syndrome ◽  
Disease Process ◽  
Massive Ascites ◽  
Elevated Liver Enzymes ◽  
Biophysical Profile ◽  
Patient Reported ◽  
Early Onset Preeclampsia ◽  
New Onset

Preeclampsia, eclampsia, and HELLP syndrome, are a continuum of a dangerous disease process that can occur in pregnancy. Preeclampsia is defined by new onset hypertension and proteinuria. In more severe cases, preeclampsia can be associated with pulmonary edema, oliguria, persistent headaches, and impaired liver function. These symptoms reveal maternal end organ damage which may result in danger to the fetus such as oligohydramnios, decreased fetal growth, and placental abruption. The defining difference between preeclampsia and eclampsia is the presence of new onset seizure activity. HELLP syndrome occurs when the mother experiences hemolysis, elevated liver enzymes, and low platelets. This syndrome is seen in about 0.6% of pregnancies. Each of these conditions (preeclampsia, eclampsia, and HELLP) increase both the fetal and maternal morbidity and mortality rates with the most definitive cure being delivery of child and placenta.A 28 year-old Caucasian, G1P0 female at 26w4d presented to OB triage on the recommendation of her physician due to elevated uric acid levels and a recorded blood pressure of 180/110. The patient reported rapid onset of weight gain, facial edema, diminished fetal movements, and frequent headaches. Although the patient denied labor symptoms, she complained of back pain and was admitted to the hospital at 26w4d for observation due to elevated blood pressures. The patient was diagnosed with preeclampsia with severe features. As her presentation progressed, the patient developed massive ascites and pulmonary edema along with decreasing platelet counts and increasing liver enzyme values. Due to decreasing biophysical profile (BPP) scores of the fetus and decompensating lab values of the mother, an emergency cesarean was performed for the safety of mother and baby.This case presentation demonstrates the progression of hypertensive disorders of pregnancy with a rare and severe presentation of early-onset preeclampsia with severe features, pulmonary edema, and massive ascites that ultimately led to class III HELLP syndrome and extreme prematurity of the infant.

scholarly journals Dysregulation of protein kinase C in adult depression and suicide: evidence from postmortem brain studies

2021 ◽  
Author(s):  
Ghanshyam N Pandey ◽  
Anuradha Sharma ◽  
Hooriyah S Rizavi ◽  
Xinguo Ren
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Mrna Expression ◽  
Postmortem Brain ◽  
Cortical Region ◽  
Cytosol Fraction ◽  
Kinase C ◽  
Pkc Isozymes

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region [Brodmann area 9 (BA9)] in 24 normal control (NC) subjects, 24 depressed suicide (DS) subjects and 12 depressed non-suicide (DNS) subjects. The levels of mRNA in the prefrontal cortex (PFC) were determined by qRT-PCR and the protein expression was determined by Western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ and PKCε and decreased protein expression either in the membrane or the cytosol fraction of PKC isozymes - PKCα, PKCβI, PKCβII and PKCδ in DS and DNS subjects compared with NC subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.

scholarly journals Identification of pluripotent cells in bovine uterus: in situ and in vitro studies

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. 317-327 ◽  
Author(s):  
Martyna Łupicka ◽  
Gabriel Bodek ◽  
Nahum Shpigel ◽  
Ehud Elnekave ◽  
Anna J Korzekwa
Keyword(s):  
Flow Cytometry ◽  
Protein Expression ◽  
Mrna Expression ◽  
Uterine Horn ◽  
Uterine Tissue ◽  
Pluripotent Cells ◽  
Flow Cytometry Assay ◽  
Myometrial Cells ◽  
Gene And Protein Expression

The aim of this study was to identify uterine pluripotent cells both in bovine uterine tissues as well in epithelial, stromal, and myometrial uterine cell populations. Moreover, the relationship of pluripotent markers expression with age and the uterine horn side was considered. Uterine tissue was collected from ipsilateral and contralateral horns (days 8–10 of the estrous cycle). Immunohistostaining for C-KIT, OCT3/4, NANOG, and SOX2 in uterine tissue was determined. mRNA expression of C-KIT, OCT3/4, NANOG and SOX2 was evaluated in uterine tissue relative to the age of the cow and uterine horn side. Gene and protein expression of these markers in the uterine luminal epithelial, stromal, and myometrial cells was evaluated by real-time PCR and western blotting respectively. The expression of pluripotent cell markers OCT3/4, NANOG, and SOX2 was identified by flow cytometry assay in epithelial, stromal, and myometrial cells. Multilineage differentiation of the bovine uterine cells was performed. mRNA expression of OCT3/4, NANOG, and SOX2 in uterine tissue was higher in the ipsilateral horn than in the contralateral horn. Flow cytometry assay revealed positive fluorescence for OCT3/4, NANOG, and SOX2 in all uterine cell types. Results showed the age-dependent expression of pluripotent markers in uterine tissue. Beside, the different expression of pluripotent cells in each horn of uterus suggests the influence of ovarian hormones on these characteristics. The highest mRNA and protein expression for pluripotent markers was observed in stromal cells among uterine cells, which indicates this population of cells as the main site of pluripotent cells in the cow uterus.

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