scholarly journals Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich's Ataxia Patients: Cellular Model of Pathology

PLoS Genetics ◽  
2010 ◽  
Vol 6 (1) ◽  
pp. e1000812 ◽  
Author(s):  
Astrid C. Haugen ◽  
Nicholas A. Di Prospero ◽  
Joel S. Parker ◽  
Rick D. Fannin ◽  
Jeff Chou ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshio Sakai ◽  
Alessandro Nasti ◽  
Yumie Takeshita ◽  
Miki Okumura ◽  
Shinji Kitajima ◽  
...  

AbstractBlood circulates throughout the body via the peripheral tissues, contributes to host homeostasis and maintains normal physiological functions, in addition to responding to lesions. Previously, we revealed that gene expression analysis of peripheral blood cells is a useful approach for assessing diseases such as diabetes mellitus and cancer because the altered gene expression profiles of peripheral blood cells can reflect the presence and state of diseases. However, no chronological assessment of whole gene expression profiles has been conducted. In the present study, we collected whole blood RNA from 61 individuals (average age at registration, 50 years) every 4 years for 8 years and analyzed gene expression profiles using a complementary DNA microarray to examine whether these profiles were stable or changed over time. We found that the genes with very stable expression were related mostly to immune system pathways, including antigen cell presentation and interferon-related signaling. Genes whose expression was altered over the 8-year study period were principally involved in cellular machinery pathways, including development, signal transduction, cell cycle, apoptosis, and survival. Thus, this chronological examination study showed that the gene expression profiles of whole blood can reveal unmanifested physiological changes.


2020 ◽  
Vol 11 ◽  
Author(s):  
Miguel A. Andrade-Navarro ◽  
Katja Mühlenberg ◽  
Eike J. Spruth ◽  
Nancy Mah ◽  
Adrián González-López ◽  
...  

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD cases vs. controls, including induction of the interferon response genes, IFITM3, IFI6 and IRF7. Our results suggest that it is possible to detect gene expression changes in blood samples from individuals with HD, which may reflect the immune pathology associated with the disease.


2018 ◽  
Vol 189 (5) ◽  
pp. 529-540 ◽  
Author(s):  
Andreas Lamkowski ◽  
Matthias Kreitlow ◽  
Jörg Radunz ◽  
Martin Willenbockel ◽  
Frank Sabath ◽  
...  

2007 ◽  
Vol 76 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Tomoko Kawai ◽  
Kyoko Morita ◽  
Kiyoshi Masuda ◽  
Kensei Nishida ◽  
Michiyo Shikishima ◽  
...  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Takanori Yaegashi ◽  
Takeshi Kato ◽  
Soichiro Usui ◽  
Naomi Kanamori ◽  
Hiroshi Furusho ◽  
...  

Introduction: Atrial fibrillation (AF) activates coagulation system leading to hypercoagulation of the blood. However, it is still unknown whether rapid atrial excitation per se affects gene expression remotely in the liver, the major source of coagulation factors and other prothrombotic molecules. Methods and Results: The AF model was created by rapid atrial pacing at the frequency of 1200 bpm in anesthetized 10-week-old Sprague-Dawley rats. The livers and peripheral blood cells were collected and analyzed after the pacing of 12 hours. Sham-operated rats underwent the identical procedure without electrical stimulation. DNA microarray revealed marked changes in hepatic gene expression after 12 hours atrial pacing. Hierarchical clustering with 13871 filtered genes or genes related to coagulation including fibrinogen, demonstrated clusters for the pacing or sham. The quantitative RT-PCR focused on prothrombotic molecules revealed that rapid atrial pacing significantly augmented the hepatic mRNA expressions of fibrinogen α, β, γ-chain, prothrombin, antithrombin-III, plasminogen, and coagulation factor X. The increase of fibrinogen protein in the liver was also confirmed by Western blotting (Figure A). We further investigated the mechanism of enhanced fibrinogen production and identified increased IL-6 mRNA expression in the peripheral blood cells by rapid atrial pacing (Figure B). IL-6 was also prominent in CD11b positive cells infiltrated in the liver, and possibly promoted STAT3 phosphorylation in the nuclei of hepatocytes (Figure C). Conclusions: The rapid atrial excitation mimicking paroxysmal AF altered the hepatic gene expressions of prothrombotic molecules. Increased fibrinogen expression in the liver was accompanied by activation of IL-6/STAT3 signaling pathway in the peripheral blood and the liver. These findings might imply the cardio-hepatic interaction in AF and provide new insight into the prevention of AF-related thromboembolism.


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