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Kunihiko Umekita, Shunichi Miyauchi, Hajime Nomura, Kazumi Umeki, Akihiko Okayama
OBJECTIVES: Damage-associated molecular patterns (DAMPs) are proposed to drive aberrant stimulation of Toll-like receptors (TLRs) in rheumatoid arthritis (RA) inflamed joints. In the current study we investigated the role of the neutrophil-derived lactoferrin (LTF), as an endogenous ligand for TLR4 in the inflammatory response of RA synovial fibroblasts (RASFs). METHODS: RASFs were stimulated with LTF, and the expressions of inflammatory cytokines in RASFs were measured...
February 11, 2019: Clinical and Experimental Rheumatology
Xuan Gao, Jiang Ming, Shiwen Liu, Bin Lai, Fang Fang, Jing Cang
The neurotoxicity of anesthetics on developing brain has been a focused issue for years. However, controversy exists between human and animal studies and surgery may be a potential reason for this. The discovery of glymphatic system, a pathway eliminating soluble substance from central nervous system (CNS), together with recent evidence that surgery-induced Aβ increase contributes to cognition dysfunction made us rethink about the influence of anesthetics on cognitive function. The function of glymphatic system was proved to be enhanced by sleep and sedation, so we assumed that under clinical situation Aβ1-40 whose accumulation played important role in cognitive dysfunction was increased by surgery and eliminated from CNS by glymphatic system...
February 11, 2019: Life Sciences
Hu Tao, Qi Xiong, Ziyun Ji, Feng Zhang, Yang Liu, Mingxin Chen
MicroRNAs (miRNAs) play key roles in mammalian folliculogenesis (a complex process in which primordial follicles develop into mature oocytes) by inhibiting mRNA translation or by inducing its degradation, while the role of miRNA in folliculogenesis and regulation mechanism remain unclear. In this study, we explored the role of the p53/miR-27a/nuclear factor of activated T-cells 5 (NFAT5) signaling axis in mouse ovarian granulosa cell proliferation. Luciferase reporter assay, overexpression, site-directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay results showed that the transcription factor p53 significantly decreased the expression level of miR-27a by binding to sites 4 (-646 to -637 bp) and 10 (-50 to -41 bp) of the miR-27a promoter...
2019: International Journal of Biological Sciences
Toru Nishinaka, Kahori Shimizu, Takeshi Miura, Chihiro Yabe-Nishimura, Tomoyuki Terada
Aldose reductase (AR), a member of aldo-keto reductase family, is the rate-limiting enzyme in the polyol pathway, and is known to play a key role in the pathogenesis of diabetic complications. AR also catalyzes the reduction of reactive aldehydes, thereby detoxifying endogenous as well as xenobiotic aldehydes in various tissues. The transcription of the AR gene was previously shown to be augmented by various stimuli including osmotic and oxidative stresses. A highly conserved region composed of an antioxidant response element (ARE), AP-1 site, and tonicity responsive enhancer (TonE) has been identified within the 5'-flanking region of the AR genes of humans, rats, and mice, which we designated as the multiple stress response region (MSRR)...
January 29, 2019: Chemico-biological Interactions
Laura G Sánchez-Lozada, Ana Andres-Hernando, Fernando E Garcia-Arroyo, Christina Cicerchi, Nanxing Li, Masanari Kuwabara, Carlos A Roncal-Jimenez, Richard J Johnson, Miguel A Lanaspa
Dietary, fructose-containing sugars have been strongly associated with the development of nonalcoholic fatty liver disease (NAFLD). Recent studies suggest that fructose also can be produced via the polyol pathway in the liver, where it may induce hepatic fat accumulation. Moreover, fructose metabolism yields uric acid, which is highly associated with NAFLD. Here, using biochemical assays, reporter gene expression, and confocal fluorescence microscopy, we investigated whether uric acid regulates aldose reductase, a key enzyme in the polyol pathway...
January 16, 2019: Journal of Biological Chemistry
Jayalakshmi Lakshmipathi, Will Wheatley, Anil Kumar, Gaelle Mercenne, Aylin R Rodan, Donald E Kohan
The inner medullary collecting duct (IMCD) produces very high levels of endothelin-1 (ET-1) that acts as an autocrine inhibitor of IMCD Na+ and water reabsorption. Recent studies suggest that IMCD ET-1 production is enhanced by extracellular hypertonicity as can occur during high salt intake. While NFAT5 has been implicated in the IMCD ET-1 hypertonicity response, no studies in any cell type have identified NFAT5 as a transcriptional regulator of the EDN1gene; the currently study examined this using a mouse IMCD cell line (IMCD3)...
January 9, 2019: American Journal of Physiology. Renal Physiology
Endre Sulyok
This article shortly outlines the evolution of hypertonia from risk factors to end-organ damage. The pathogenetic role of salt intake is underlined and in the light of recent clinical and experimental observations, the importance of renal and extrarenal mechanism in the development of salt-sensitive hypertension is analysed. The generally accepted concept that the inefficient renal sodium excretion and the subsequent expansion of the extracellular space is the major factor in blood pressure elevation is challenged...
January 2019: Orvosi Hetilap
Cecilia I Casali, Luciana C Erjavec, María Del Carmen Fernández-Tome
NF-κB and TonEBP belong to the Rel-superfamily of transcription factors. Several specific stimuli, including hypertonicity which is a key factor for renal physiology, are able to activate them. It has been reported that, after hypertonic challenge, NF-κB activity can be modulated by TonEBP, considered as the master regulator of transcriptional activity in the presence of changes in environmental tonicity. In the present work we evaluated whether hypertonicity-induced gene transcription mediated by p65/RelA and TonEBP occurs by an independent action of each transcription factor or by acting together...
December 2018: Heliyon
Joy L Britten, Minnie Malik, Terrence D Lewis, William H Catherino
Nuclear factor of activated T-cells (NFAT5) is a tissue specific, osmoadaptive transcription factor essential for the control of hydration homeostasis in mammalian cells. Nuclear factor of activated T-cells regulates osmolyte transporters aldo-keto reductase family 1 member B1 (AKR1B1) and solute carrier family 5 member 3 (SLC5A3) to maintain fluid equilibrium in cells. The osmotic potential of the extracellular matrix of leiomyomas is attributed to the role of proteoglycans. In leiomyoma cells, NFAT5 is overexpressed compared to myometrial cells...
December 19, 2018: Reproductive Sciences
Jae-Ung Lee, Li-Kyung Kim, Je-Min Choi
The nuclear factor of activated T cells (NFAT) family of transcription factors, which includes NFAT1, NFAT2, and NFAT4, are well-known to play important roles in T cell activation. Most of NFAT proteins are controlled by calcium influx upon T cell receptor and costimulatory signaling results increase of IL-2 and IL-2 receptor. NFAT3 however is not shown to be expressed in T cells and NFAT5 has not much highlighted in T cell functions yet. Recent studies demonstrate that the NFAT family proteins involve in function of lineage-specific transcription factors during differentiation of T helper 1 (Th1), Th2, Th17, regulatory T (Treg), and follicular helper T cells (Tfh)...
2018: Frontiers in Immunology
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
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