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https://www.readbyqxmd.com/read/28818208/catecholamine-dependent-%C3%AE-adrenergic-signaling-in-a-pluripotent-stem-cell-model%C3%A2-of-takotsubo-cardiomyopathy
#1
Thomas Borchert, Daniela Hübscher, Celina I Guessoum, Tuan-Dinh D Lam, Jelena R Ghadri, Isabel N Schellinger, Malte Tiburcy, Norman Y Liaw, Yun Li, Jan Haas, Samuel Sossalla, Mia A Huber, Lukas Cyganek, Claudius Jacobshagen, Ralf Dressel, Uwe Raaz, Viacheslav O Nikolaev, Kaomei Guan, Holger Thiele, Benjamin Meder, Bernd Wollnik, Wolfram-Hubertus Zimmermann, Thomas F Lüscher, Gerd Hasenfuss, Christian Templin, Katrin Streckfuss-Bömeke
BACKGROUND: Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. OBJECTIVES: The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS...
August 22, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28771574/acute-and-chronic-effects-of-exercise-on-mrna-expression-in-the-skeletal-muscle-of-two-mouse-models-of-peripheral-artery-disease
#2
Hiroki Nagase, Shuhei Yao, Shota Ikeda
Endurance exercise improves walking performance in patients with peripheral artery disease (PAD), which is characterized by skeletal muscle dysfunction caused by lower extremity ischemia. Although transcriptional analyses of exercise-induced changes in normal animals and healthy volunteers have been reported, no detailed study has explored exercise-induced alterations in gene expression in PAD animal models. Here, we determined the acute and chronic effects of exercise on mRNA expression in the skeletal muscles of two mouse models of PAD...
2017: PloS One
https://www.readbyqxmd.com/read/28754437/inactivation-of-the-orphan-nuclear-receptor-nr4a1-contributes-to-apoptosis-induction-by-fangchinoline-in-pancreatic-cancer-cells
#3
Hyo-Seon Lee, Stephen Safe, Syng-Ook Lee
Previous studies have demonstrated that the orphan nuclear receptor NR4A1 is overexpressed in human pancreatic cancer and antagonizing this receptor promotes apoptosis and inhibits pancreatic cancer cells and tumor growth. In the present study, we identified fangchinoline, a bisbenzyltetrahydroisoquinoline alkaloid from Stephania tetrandra, as a new inactivator of nuclear NR4A1 and demonstrated that fangchinoline inhibits cell proliferation and induces apoptosis, in part, via the NR4A1-dependent pro-apoptotic pathways in human pancreatic cancer cells...
July 25, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733346/regulation-and-action-of-early-growth-response-1-in-bovine-granulosa-cells
#4
Peng Han, Hilda Guerrero-Netro, Anthony Estienne, Binyun Cao, Christopher Price
Fibroblast growth factors (FGF) modify cell proliferation and differentiation through receptor tyrosine kinases, which stimulate the expression of transcription factors including members of the early growth response (EGR) family. In ovarian granulosa cells, most FGFs activate typical response genes, although the role of EGR proteins has not been described. In the present study, we determined the regulation of EGR mRNA by FGFs and explored the role of EGR1 in the regulation of FGF response genes. Addition of FGF1, FGF2, FGF4 or FGF8b increased EGR1 and EGR3 mRNA levels, whereas FGF18 increased only EGR1 mRNA abundance...
July 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28713898/identification-of-potential-biomarkers-and-therapeutic-targets-for-human-iga-nephropathy-and-hypertensive-nephropathy-by-bioinformatics-analysis
#5
Yingchun Cui, Shengmao Liu, Wenpeng Cui, Dan Gao, Wenhua Zhou, Ping Luo
In order to further elucidate the potential correlations and treatments of IgA nephropathy (IgAN) and hypertensive nephropathy (HT), bioinformatics analysis of IgAN and HT was performed. The mRNA expression profiles of human renal biopsy samples from patients with IgAN, patients with HT and pre‑transplant healthy living controls (LD) were downloaded from the Gene Expression Omnibus database. Then, the differentially expressed genes (DEGs) were identified and functions of DEGs were analyzed. Finally, the regulatory networks containing DEGs and related‑transcription factors (TFs) were constructed using Cytoscape software...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28674186/tgf%C3%AE-nr4a1-inducible-breast-cancer-cell-migration-and-epithelial-to-mesenchymal-transition-is-p38%C3%AE-mapk14-dependent
#6
Erik Hedrick, Stephen Safe
Transforming growth factor β (TGFβ)-induced migration of triple negative breast cancer (TNBC) cells is dependent on nuclear export of the orphan receptor NR4A1 which plays a role in proteasome-dependent degradation of SMAD7. In this study, we show that TGFβ induces p38α (MAPK14) which in turn phosphorylates NR4A1, resulting in nuclear export of the receptor. TGFβ/p38α and NR4A1 also play essential roles in the induction of epithelial to mesenchymal transition (EMT) and induction of β-catenin in TNBC cells, and these TGFβ-induced responses and nuclear export of NR4A1 are blocked by NR4A1 antagonists, the p38 inhibitor SB202190, kinase dead [p38(KD)] and dominant negative [p38(DN)] forms of p38α...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28635301/stem-cell-mediated-paracrine-signaling-alters-fibroplasia-in-human-vocal-fold-fibroblasts-in-vitro
#7
Nao Hiwatashi, Renjie Bing, Iv Kraja, Ryan C Branski
OBJECTIVES: Interactions between mesenchymal stem cells (MSCs) and native vocal fold fibroblasts (VFFs) have not been described in spite of promising preliminary data regarding the effects of MSCs on vocal fold repair in vivo. The current study employed a conditioned media (CM) model to investigate the paracrine effects of bone marrow-derived mesenchymal stem cells (BMSCs) on VFFs. METHODS: Human VFFs were treated with transforming growth factor-β1 (TGF-β1; 10 ng/mL), CM from human BMSCs following 48 hours of TGF-β1 stimulation, or CM+TGF-β1...
August 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28622293/sumo-triggered-ubiquitination-of-nr4a1-controls-macrophage-cell-death
#8
Long Zhang, Feng Xie, Juan Zhang, Peter Ten Dijke, Fangfang Zhou
Nuclear receptor NR4A1 has been implicated as a key regulator in a wide range of pathophysiological responses. As an immediate early response gene, NR4A1 can be rapidly and potently induced by a variety of stimuli. Its induction is followed by its rapid degradation, but the mechanism by which NR4A1 is degraded remains poorly understood. Here we show that nuclear receptor NR4A1 is sumoylated by SUMO2/3. Upon poly-SUMO modification, NR4A1 can be targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28599476/identification-of-gene-markers-associated-with-metastasis-in-clear-cell-renal-cell-carcinoma
#9
Hailing Yang, Pengfei Huo, Guozhang Hu, Bo Wei, Dalian Kong, Hongjun Li
The present study aimed to screen potential target genes for the early diagnosis and treatment of early metastatic clear cell renal cell carcinoma (ccRCC) using the microarray data of early metastatic and non-metastatic ccRCC samples. The DNA microarray dataset GSE47352 was downloaded from Gene Expression Omnibus and included 4 early metastatic and 5 non-metastatic ccRCC samples. Differentially expressed genes (DEGs) were screened using the limma package. Then, pheatmap package was used to conduct two-way clustering for the DEGs...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28581197/nr4a1-is-an-endogenous-inhibitor-of-vocal-fold-fibrosis
#10
Nao Hiwatashi, Renjie Bing, Iv Kraja, Ryan C Branski
OBJECTIVES/HYPOTHESIS: NR4A1 was recently identified as an endogenous inhibitor of transforming growth factor (TGF)-β-induced fibrosis, and the role of this nuclear receptor has not been elucidated in tissue health or the response to injury in the vocal folds. Given the clinical implications of vocal fold fibrosis, we investigated NR4A1 expression during vocal fold wound healing in vivo and the regulatory roles of NR4A1 on vocal fold fibroblasts (VFFs) in vitro with the ultimate goal of developing targeted therapies for this challenging patient population...
June 5, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28514727/nuclear-receptor-nr4a1-is-a-tumor-suppressor-down-regulated-in-triple-negative-breast-cancer
#11
Hongmei Wu, Jiong Bi, Yan Peng, Lei Huo, Xiaobin Yu, Zhihui Yang, Yunyun Zhou, Li Qin, Yixiang Xu, Lan Liao, Yang Xie, Orla M Conneely, Jos Jonkers, Jianming Xu
The nuclear receptor (NR) superfamily contains hormone-inducible transcription factors that regulate many physiological and pathological processes through regulating gene expression. NR4A1 is an NR family member that still does not have an identified endogenous ligand, and its role in cancer is also currently unclear and controversial. In this study, we aimed to define the expression profiles and specific role of NR4A1 in the highly malignant triple-negative breast cancer (TNBC), which still lacks available targeted therapies...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514690/genomic-characterization-of-murine-monocytes-reveals-c-ebp%C3%AE-transcription-factor-dependence-of-ly6c-cells
#12
Alexander Mildner, Jörg Schönheit, Amir Giladi, Eyal David, David Lara-Astiaso, Erika Lorenzo-Vivas, Franziska Paul, Louise Chappell-Maor, Josef Priller, Achim Leutz, Ido Amit, Steffen Jung
Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. Murine Ly6C(+) monocytes display developmental plasticity and are recruited to complement tissue-resident macrophages and dendritic cells on demand. Murine vascular Ly6C(-) monocytes patrol the endothelium, act as scavengers, and support vessel wall repair. Here we characterized population and single cell transcriptomes, as well as enhancer and promoter landscapes of the murine monocyte compartment...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#13
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
Purpose: EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on multiple myeloma and prostate cancer.Experimental Design:In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in multiple myeloma cell lines, primary patient cells, and in a xenograft model...
August 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28418095/the-nuclear-orphan-receptor-nr4a1-regulates-%C3%AE-1-integrin-expression-in-pancreatic-and-colon-cancer-cells-and-can-be-targeted-by-nr4a1-antagonists
#14
Erik Hedrick, Syng-Ook Lee, Stephen Safe
β1-Integrin is highly expressed and is a negative prognostic factor for colon and pancreatic cancer patients and the gene plays a functional role in cell migration and invasion. In this study, we demonstrate that β1-integrin expression is regulated in pancreatic and colon cancer cells by the pro-oncogenic orphan nuclear receptor 4A1 (NR4A1, Nur77, TR3) and knockdown of this receptor by RNA interference decreases β1-integrin protein and mRNA expression, α5-integrin, and also expression of β1-integrin-dependent phosphorylation of FAK (pFak)...
September 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28412351/effect-of-apoa4-on-serpina3-mediated-by-nuclear-receptors-nr4a1-and-nr1d1-in-hepatocytes
#15
Yupeng Zhang, Jing He, Jing Zhao, Min Xu, Danwen Lou, Patrick Tso, Zongfang Li, Xiaoming Li
ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28411187/the-nuclear-receptor-nr4a1-acts-as-a-microglia-rheostat-and-serves-as-a-therapeutic-target-in-autoimmune-driven-central-nervous-system-inflammation
#16
Tobias Rothe, Natacha Ipseiz, Maria Faas, Stefanie Lang, Francesc Perez-Branguli, Daniel Metzger, Hiroshi Ichinose, Beate Winner, Georg Schett, Gerhard Krönke
Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarization of microglia. In steady-state microglia, ubiquitous neuronal-derived stress signals such as ATP induced expression of this NR, which contributed to the maintenance of a resting and noninflammatory microglia phenotype...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28376367/injectable-nanofibrous-spongy-microspheres-for-nr4a1-plasmid-dna-transfection-to-reverse-fibrotic-degeneration-and-support-disc-regeneration
#17
Ganjun Feng, Zhanpeng Zhang, Ming Dang, Xiaojin Zhang, Yasmine Doleyres, Yueming Song, Di Chen, Peter X Ma
Safe and efficient gene therapy is highly desired for controlling pathogenic fibrosis of nucleus pulposus (NP) tissue, which would result in intervertebral disc (IVD) degeneration and disability if left untreated. In this work, a hyperbranched polymer (HP) with high plasmid DNA (pDNA) binding affinity and negligible cytotoxicity is synthesized, which can self-assemble into nano-sized polyplexes with a "double shell" structure that can transfect pDNA into NP cells with very high efficiency. These polyplexes are then encapsulated in biodegradable nanospheres (NS) to enable two-stage delivery: 1) temporally-controlled release of pDNA-carrying polyplexes and 2) highly efficient delivery of pDNA into cells by the released polyplexes...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28342843/the-stress-response-molecule-nr4a1-resists-ros-induced-pancreatic-%C3%AE-cells-apoptosis-via-wt1
#18
Chen Zong, Dandan Qin, Cong Yu, Peng Gao, Jicui Chen, Sumei Lu, Yuchao Zhang, Yuantao Liu, Yingfeng Yang, Zeqing Pu, Xia Li, Yuchang Fu, Qingbo Guan, Xiangdong Wang
Pancreatic β-cells often face endoplasmic reticulum stress and/or ROS-associated oxidative stress under adverse conditions. Our previous work has verified that NR4A1 protects pancreatic β-cells from ER-stress induced apoptosis. However, It remains unknown whether NR4A1 is able to protect pancreatic β-cells against ROS-associated oxidative stress. In the present study, our data showed that NR4A1 protein expression rapidly increased in MIN6 cells upon H2O2 treatment, and overexpression of NR4A1 in MIN6 cells conferred resistance to cell apoptosis induced by H2O2...
March 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28337303/the-involvement-and-possible-mechanism-of-nr4a1-in-chondrocyte-apoptosis-during-osteoarthritis
#19
Xinge Shi, Hui Ye, Xuedong Yao, Yanzheng Gao
Osteoarthritis (OA) is a joint disease caused by the breakdown of joint cartilage and underlying bone, and places great burdens to daily life of patients. Nuclear orphan receptor nuclear receptor subfamily 4, group A, member 1 (NR4A1) is vital for cell apoptosis, but little is known about its role in OA. This study aims to reveal the expression and function of NR4A1 during OA chondrocyte apoptosis. NR4A1 expression by qRT-PCR and western blot, and chondrocyte apoptosis by TUNEL assay were detected in normal and OA joint cartilage...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28302649/endothelial-protective-monocyte-patrolling-in-large-arteries-intensified-by-western-diet-and-atherosclerosis
#20
Amado Quintar, Sara McArdle, Dennis Wolf, Alex Marki, Erik Ehinger, Melanie Vassallo, Jacqueline Miller, Zbigniew Mikulski, Klaus Ley, Konrad Buscher
RATIONALE: Nonclassical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Because of technical challenges, it is currently not established how patrolling occurs in large arteries. OBJECTIVE: This study was undertaken to elucidate the molecular, migratory, and functional phenotypes of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic, and atherosclerotic conditions...
May 26, 2017: Circulation Research
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