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Consuelo Pasten, Cristóbal Alvarado, Jocelyn Rocco, Luis Contreras, Paula Aracena, Jéssica Liberona, Cristian Suazo, Luis Fernando Michea, Carlos E Irarrázabal
Upon renal ischemia-reperfusion (IR) injury, recruitment of neutrophils during the inflammatory process promotes local generation of oxygen and nitrogen reactive species which, in turn, are likely to exacerbate tissue damage. The mechanism by which iNOS is involved in IR has not been completely elucidated. In this work, the selective iNOS inhibitor L-N6 -(1-iminoethyl)lysine (L-NIL) and the NOS substrate L-Arginine (L-Arg), were employed to understand the role of NOS activity on the expression of particular target genes and the oxidative stress elicited after a 30 min of bilateral renal ischemia, followed by 48h reperfusion in BALB/c mice...
December 5, 2018: American Journal of Physiology. Renal Physiology
A Sadowska, T Kameda, O Krupkova, K Wuertz-Kozak
Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD's extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation...
November 19, 2018: European Cells & Materials
Xing-Liang Yang, Xin Wang, Bi-Wen Peng
Nuclear factor of activated T cells 5 (NFAT5) has recently been classified as a new member of the Rel family. In addition, there are 5 more well-defined members (NF-κB and NFAT1-4) in the Rel family, which participate in regulating the expression of immune and inflammatory response-related genes. NFAT5 was initially identified in renal medullary cells where it regulated the expression of osmoprotective-related genes during the osmotic response. Many studies have demonstrated that NFAT5 is highly expressed in the nuclei of neurons in fetal and adult brains...
November 2, 2018: Developmental Neuroscience
Elizabeth A Aisenbrey, Stephanie J Bryant
Mesenchymal stem cells (MSCs) are promising for cartilage regeneration, but readily undergo terminal differentiation. The aim of this study was two-fold: a) investigate physiochemical cues from a cartilage-mimetic hydrogel under dynamic compressive loading on MSC chondrogenesis and hypertrophy and b) identify whether Smad signaling and p38 MAPK signaling mediate hypertrophy during MSC chondrogenesis. Human MSCs were encapsulated in photoclickable poly(ethylene glycol) hydrogels containing chondroitin sulfate and RGD, cultured under dynamic compressive loading or free swelling for three weeks, and evaluated by qPCR and immunohistochemistry...
October 25, 2018: Biomaterials
Caroline Arnold, Anja Feldner, Maren Zappe, Dorde Komljenovic, Carolina De La Torre, Philipp Ruzicka, Markus Hecker, Wolfgang Neuhofer, Thomas Korff
The arterial wall adapts to alterations in blood flow and pressure by remodeling the cellular and extracellular architecture. Biomechanical stress of vascular smooth muscle cells (VSMCs) in the media is thought to precede this process and promote their activation and subsequent proliferation. However, molecular determinants orchestrating the transcriptional phenotype under these conditions have been insufficiently studied. We identified the transcription factor, nuclear factor of activated T cells 5 (NFAT5; or tonicity enhancer-binding protein) as a crucial regulatory element of mechanical stress responses of VSMCs...
November 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Guihua Ge, Dongli Yang, Ya Tan, Ying Chen, Dongmei Jiang, Anan Jiang, Qiang Li, Yihui Liu, Zhijun Zhong, Xuewei Li, Shunhua Zhang, Li Zhu
The development of skeletal muscle is a complex process including myoblasts proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at post-transcriptional level. Increasing evidences indicate that miRNAs are important regulators in myogenic processes. Here, we reported that the expression of miR-10b-5p steadily decreased during myoblasts proliferation, but significantly increased during myoblasts differentiation. The over-expression of miR-10b-5p promoted myoblasts proliferation and blunted myofiber formation in C2C12 cells, while miR-10b-5p down-regulation showed an opposite result...
October 18, 2018: Bioscience, Biotechnology, and Biochemistry
Michael Fähling, Alexander Paliege, Sofia Jönsson, Mediha Becirovic-Agic, Jacqueline M Melville, Trude Skogstrand, Michael Hultström
The aim was to identify new targets that regulate gene expression at the post-transcriptional level in Angiotensin II (ANGII)-mediated hypertension. Heparin affinity chromatography was used to enrich nucleic acid-binding proteins from kidneys of two-kidney, one-clip (2K1C) hypertensive Wistar rats. The experiment was repeated with 14 days ANGII infusion using Alzet osmotic mini pumps, with or without ANGII receptor AT1a inhibition using Losartan in the drinking water. Mean arterial pressure increased after 2K1C or ANGII infusion and was inhibited with Losartan...
October 17, 2018: American Journal of Physiology. Renal Physiology
Maria Buxadé, Hector Huerga Encabo, Marta Riera-Borrull, Lucía Quintana-Gallardo, Pilar López-Cotarelo, Mónica Tellechea, Sara Martínez-Martínez, Juan Miguel Redondo, Juan Martín-Caballero, Juana María Flores, Elena Bosch, José Luis Rodríguez-Fernández, Jose Aramburu, Cristina López-Rodríguez
MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type-specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4+ T lymphocytes and attenuated capacity to elicit graft rejection in vivo...
November 5, 2018: Journal of Experimental Medicine
Jana Kleiner, Margrit Hollborn, Peter Wiedemann, Andreas Bringmann
Purpose: Systemic hypertension is a risk factor of neovascular age-related macular degeneration; consumption of dietary salt resulting in extracellular hyperosmolarity is a main cause of hypertension. Extracellular hyperosmolarity was shown to induce expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), in RPE cells. The aim of the present study was to determine whether the hyperosmotic expression of growth factor genes in RPE cells is mediated by activator protein-1 (AP-1), and whether c-Fos and c-Jun genes are regulated by extracellular osmolarity...
2018: Molecular Vision
Dong-Ho Kim, Kye-Seong Kim, Suresh Ramakrishna
Malignant melanoma is one of the most fatal and aggressive skin cancers, originating from pigment-containing melanocytes. Despite progress in clinical research, treatment options for malignant melanoma have been limited. The nuclear factor of activated T-cell 5 (NFAT5), originally identified as tonicity regulated transcription factor Ton/EBP, is now known as a carcinogenic gene in several types of cancer pathology. In this study, we knocked down NFAT5 to investigate its role in melanoma cancer. shRNA-mediated knockdown of NFAT5 led to a significant decrease in cell proliferation in vitro...
November 2, 2018: Biochemical and Biophysical Research Communications
Geyan Wu, Lixue Cao, Jinrong Zhu, Zhanyao Tan, Miaoling Tang, Ziwen Li, Yameng Hu, Ruyuan Yu, Shuxia Zhang, Libing Song, Jun Li
PURPOSE: The development of resistance to platinum-based chemotherapy remains the unsurmountable obstacle in cancer treatment and consequently leads to tumor relapse. This study aims to investigate the mechanism by which loss of RBMS3 induced chemoresistance in epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN: Fluorescence in situ hybridization and immunochemistry were used to determine deletion frequency and expression of RBMS3 in 15 clinical EOC tissues and 150 clinicopathologically characterized EOC specimens...
October 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Vanessa Pereira, Queensta Millet, Jose Aramburu, Cristina Lopez-Rodriguez, Claire Gaveriaux-Ruff, John N Wood
Background: Functional deletion of the Scn9a (sodium voltage-gated channel alpha subunit 9) gene encoding sodium channel Nav1.7 makes humans and mice pain-free. Opioid signalling contributes to this analgesic state. We have used pharmacological and genetic approaches to identify the opioid receptors involved in this form of analgesia. We also examined the regulation of proenkephalin expression by the transcription factor Nfat5 that binds upstream of the Penk gene. Methods: We used specific µ-, δ- and κ-opioid receptor antagonists alone or in combination to examine which opioid receptors were necessary for Nav1...
2018: Wellcome Open Research
Sergei N Orlov, Aleksandra Shiyan, Francis Boudreault, Olga Ponomarchuk, Ryszard Grygorczyk
The plasma membrane plays a prominent role in the regulation of cell volume by mediating selective transport of extra- and intracellular osmolytes. Recent studies show that upstream sensors of cell volume changes are mainly located within the cytoplasm that displays properties of a hydrogel and not in the plasma membrane. Cell volume changes occurring in anisosmotic medium as well as in isosmotic environment affect properties of cytoplasmic hydrogel that, in turn, trigger rapid regulatory volume increase and decrease (RVI and RVD)...
2018: Current Topics in Membranes
Katharina Essig, Nina Kronbeck, Joao C Guimaraes, Claudia Lohs, Andreas Schlundt, Anne Hoffmann, Gesine Behrens, Sven Brenner, Joanna Kowalska, Cristina Lopez-Rodriguez, Jacek Jemielity, Helmut Holtmann, Kristin Reiche, Jörg Hackermüller, Michael Sattler, Mihaela Zavolan, Vigo Heissmeyer
The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem-loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3'-UTR shows that six stem-loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem-loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition...
September 19, 2018: Nature Communications
Hong Zhu, Wei Cao, Peng Zhao, Jieyu Wang, Yuying Qian, Yun Li
Hyperosmotic stress may be initiated during a diverse range pathological circumstances, which in turn results in tissue damage. In this process, the activation of survival signaling, which has the capacity to restore cell homeostasis, determines cell fate. Autophagy is responsible for cell survival and is activated by various pathological stimuli. However, its interplay with hyperosmotic stress and its effect on terminally differentiated cardiac myocytes is unknown. Nuclear factor of activated T‑cells 5 (NFAT5), an osmo‑sensitive transcription factor, mediates the expression of cell survival associated‑genes under hyperosmotic conditions...
September 12, 2018: International Journal of Molecular Medicine
Matthew R Hart, Donovan J Anderson, Christopher C Porter, Tobias Neff, Michael Levin, Marshall S Horwitz
PAX5, one of nine members of the mammalian paired box (PAX) family of transcription factors, plays an important role in B cell development. Approximately one-third of individuals with pre-B acute lymphoblastic leukemia (ALL) acquire heterozygous inactivating mutations of PAX5 in malignant cells, and heterozygous germline loss-of-function PAX5 mutations cause autosomal dominant predisposition to ALL. At least in mice, Pax5 is required for pre-B cell maturation, and leukemic remission occurs when Pax5 expression is restored in a Pax5-deficient mouse model of ALL...
September 2018: PLoS Genetics
Maren Zappe, Anja Feldner, Caroline Arnold, Carsten Sticht, Markus Hecker, Thomas Korff
Vascular cells are continuously exposed to mechanical stress that may wreak havoc if exceeding physiological levels. Consequently, mechanisms facing such a challenge are indispensable and contribute to the adaptation of the cellular phenotype. To this end, vascular smooth muscle cells (VSMCs) activate mechanoresponsive transcription factors promoting their proliferation and migration to initiate remodeling the arterial wall. In mechanostimulated VSMCs, we identified nuclear factor of activated T-cells 5 (NFAT5) as transcriptional regulator protein and intended to unravel mechanisms controlling its expression and nuclear translocation...
2018: Frontiers in Physiology
Ting Guo, Hao Ding, Hui Jiang, Nirong Bao, Liwu Zhou, Jianning Zhao
BACKGROUND/AIMS: MicroRNAs (miRNAs) have been reported to be involved in Rheumatoid arthritis (RA) pathogenesis and prognosis. However, little is known about the disease mechanism in RA. Here, we aim to investigate the potential association between miR-338-5p and NFAT5 in RA. METHODS: Aberrant expression of miR-338-5p in RA tissues and rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) compared to the normal were determined by RT-qPCR. Cell viability was determined using the CCK-8 assay, and cell apoptosis was analyzed via Annexin V-FITC/PI double staining and was detected using flow cytometry...
2018: Cellular Physiology and Biochemistry
Margrit Hollborn, Charlotte Ackmann, Heidrun Kuhrt, Fabian Doktor, Leon Kohen, Peter Wiedemann, Andreas Bringmann
Purpose: Variants of complement factor genes, hypoxia and oxidative stress of the outer retina, and systemic hypertension affect the risk of age-related macular degeneration. Hypertension often results from the high intake of dietary salt that increases extracellular osmolarity. We determined the effects of extracellular hyperosmolarity, hypoxia, and oxidative stress on the expression of complement genes in cultured (dedifferentiated) human RPE cells and investigated the effects of C9 siRNA and C9 protein on RPE cells...
2018: Molecular Vision
Maria Florencia Albertoni Borghese, Sandra Hope, Maria Del Carmen Ortiz, Magalí Barchuk, Camila Kessler, Carlos Davio, Marcelo Vatta, Mónica Majowicz
AIMS: The aim of the present study was to evaluate the regulation of Aquaporin-2 (AQP2) water channel in the kidney of one-kidney, one-clip rats (Goldblatt-1 model). In addition, some mechanisms that underlie the role of AQP2 in the Goldblatt-1 model were evaluated. MAIN METHODS: Sprague-Dawley rats were divided in three groups: control two-kidney, no clip (C, 2 K-NC); nephrectomized one-kidney, no clip (N, 1 K-NC) and Goldblatt one-kidney, one-clip (G, 1 K-1C)...
September 1, 2018: Life Sciences
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