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American Journal of Physiology. Cell Physiology

Hojin Kang, Zhigang Hong, Ming Zhong, Jennifer Klomp, Kayla J Bayless, Dolly Mehta, Andrei V Karginov, Guochang Hu, Asrar B Malik
Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here we investigated the pro-angiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine-1-phosphate while Piezo1 activation by a selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis...
November 14, 2018: American Journal of Physiology. Cell Physiology
Man Si, Krystle Trosclair, Kathryn A Hamilton, Edward Glasscock
Voltage-gated Kv1.1 potassium channel α-subunits, encoded by the Kcna1 gene, have traditionally been regarded as neural-specific with no expression or function in the heart. However, recent data revealed Kv1.1 subunits are expressed in atria where they may have an overlooked role in controlling repolarization and arrhythmia susceptibility independent of the nervous system. To explore this concept in more detail and to identify functional and molecular effects of Kv1.1 channel impairment in the heart, atrial cardiomyocyte patch-clamp electrophysiology and gene expression analyses were performed using Kcna1 knockout ( Kcna1-/- ) mice...
November 14, 2018: American Journal of Physiology. Cell Physiology
Dong-Mei Wu, Xin Wen, Xin-Rui Han, Shan Wang, Yong-Jian Wang, Min Shen, Shao-Hua Fan, Juan Zhuang, Zi-Feng Zhang, Qun Shan, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Jun Lu, Yuan-Lin Zheng
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, affecting the quality of life of millions of people worldwide. The current study aims to determine the relationship between microRNA-143 (miR-143) and CXCL13, and whether it influences the pathogenesis of myasthenia gravis (MG). Thymus specimens were resected from patients with thymic hyperplasia combined MG, and then infused into normal mouse cavities to establish MG mice models. Immunohistochemistry, RT-qPCR, in situ hybridization detection, and Western blot analysis were employed to identify the expression of miR-143 and CXCL13 in MG and normal mice...
November 7, 2018: American Journal of Physiology. Cell Physiology
Jianming Guo, Haidi Hu, Jolanta Gorecka, Hualong Bai, Hao He, Roland Assi, Toshihiko Isaji, Tun Wang, Ocean Setia, Lara Lopes, Yongquan Gu, Alan Dardik
We have previously shown that bone marrow-derived mesenchymal stem cells (BMSC) accelerate wound healing in a diabetic mouse model. We hypothesized that adipose tissue-derived stem cells (ADSC), of greater translational potential to human therapy, similarly improve diabetic wound healing. In this study, in vitro, the characterization and function of murine ADSC and BMSC, or human diabetic and non-diabetic ADSC were evaluated by flow cytometry, cell viability, and VEGF expression. In vivo, biomimetic collagen scaffolds containing murine ADSC or BMSC were used to treat diabetic wounds on mice, and human diabetic ADSC or non-diabetic ADSC were used to treat back wounds on nude mice; wound healing was evaluated by area, local VEGF expression, and angiogenesis...
November 7, 2018: American Journal of Physiology. Cell Physiology
Qiang Lou, Yanzhong Hu, Yuanfang Ma, Zheng Dong
RNA-induced silencing complex (RISC) is formed during RNA interference (RNAi), while stress granules (SG) are assembled in response to cellular stress. Here, we demonstrate an interesting connection between RISC and SG that may involve Argonaute 2 (Ago2), a core component of RISC. We analyzed SG induction by arsenite, the commonly used SG inducer. SG formation was suppressed in Hsf1 or Hif1α shRNA -transfected cells, but not in Hsf1 or Hif1α -knockout cells, suggesting that RNAi per se (rather than gene deficiency) may account for the suppressive effect on SG...
November 7, 2018: American Journal of Physiology. Cell Physiology
Nathaniel J Hart, Craig Weber, Klearchos K Papas, Sean W Limesand, Josef Vagner, Ronald M Lynch
Linking two pharmacophores that bind different cell surface receptors into a single molecule can enhance cell-targeting specificity to cells that express the complementary receptor pair. In this report, we developed and tested a synthetic multivalent ligand consisting of glucagon-like peptide-1 (GLP-1) linked to glibenclamide (Glb) for signaling efficacy in β-cells. Expression of receptors for these ligands, as a combination, are relatively specific to the β-cell in the pancreas. The multivalent GLP-1/Glb increased both intracellular cAMP and Ca2+ , although Ca2+ responses were significantly depressed compared to the monomeric Glb...
November 7, 2018: American Journal of Physiology. Cell Physiology
Zihui Zhou, Yuanshan Lu, Yao Wang, Lin Du, Yunpeng Zhang, Jie Tao
Osteoporosis is a progressive bone disease characterized by decreased bone mass and density which usually parallels a reduced antioxidative capacity and increased ROS formation. Adipose-derived mesenchymal stem cells (ADMSCs), a population of self-renewing multipotent cells, are a well-recognised source of potential bone precursors with significant clinical potential for tissue regeneration. We previously showed that overexpressing stearoyl-CoA desaturase 1 (SCD-1) promotes osteogenic differentiation of mesenchymal stem cells (MSCs)...
October 31, 2018: American Journal of Physiology. Cell Physiology
Changjun Yang, Kimberly E Hawkins, Sylvain Dore, Eduardo Candelario-Jalil
The blood-brain barrier (BBB), also known as the neurovascular unit, is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and the central nervous system. Disruption of the BBB plays an important role in the development of neurological dysfunction in ischemic stroke. Blood-borne substances and cells have restricted access to the brain due to the presence of tight junctions between the endothelial cells of the BBB. Following stroke, there is loss of BBB tight junctions integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality...
October 31, 2018: American Journal of Physiology. Cell Physiology
Katarzyna K Krawczyk, Gry Freja Skovsted, Ljubica Perisic, Rasmus Dreier, Jais Oliver Berg, Ulf Hedin, Catarina Rippe, Karl Sward
The endothelin type B receptor (ETB or EDNRB) is highly plastic and is upregulated in smooth muscle cells (SMCs) by arterial injury and following organ culture. We hypothesized that this transcriptional plasticity may arise, in part, because EDNRB is controlled by a balance of transcriptional inputs from myocardin-related transcription factors (MRTFs) and ternary complex factors (TCFs). We found significant positive correlations between the TCFs ELK3 and FLI1 versus EDNRB in human arteries. The MRTF MKL2 also correlated with EDNRB...
October 17, 2018: American Journal of Physiology. Cell Physiology
Scott M O'Grady
Mucociliary clearance is critically important in protecting the airways from infection and from the harmful effects of smoke and various inspired substances known to induce oxidative stress and persistent inflammation. An essential feature of the clearance mechanism involves regulation of the periciliary liquid layer (PCL) on the surface of the airway epithelium, which is necessary for normal ciliary beating and for maintaining mucus hydration. The underlying ion transport processes associated with airway surface hydration include ENaC-dependent Na+ absorption occurring in parallel with CFTR and Ca2+ -activated Cl- channel-dependent anion secretion, which are coordinately regulated to control the depth of the PCL layer...
October 10, 2018: American Journal of Physiology. Cell Physiology
Clarisse Fuster, Romane Idoux, Christine Berthier, Vincent Jacquemond, Bruno Allard
High metabolic activity and existence of a large transmembrane inward electrochemical gradient for H+ at rest promote intracellular acidification of skeletal muscle. Exchangers and cotransports efficiently contend against accumulation of intracellular H+ and associated deleterious effects on muscle functions. Voltage-gated H+ channels have also been found to represent another H+ extrusion pathway in cultured muscle cells. Up to now, the skeletal muscle cell was therefore the unique vertebrate excitable cell in which voltage-gated H+ currents have been described...
October 3, 2018: American Journal of Physiology. Cell Physiology
Qiong Chen, Yuanyuan Hang, Tingting Zhang, Li Tan, Shuangdi Li, Yuli Jin
Endometriosis has been initially described as endometrial-like tissue outside of the uterine cavity. Mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway playing an important role in the regulation of cell proliferation, apoptosis and migration has been found to be activated in endometriosis. However, the regulation of MEK/ERK signaling pathway in endometriosis has not been fully understood. In this study, primary-cultured endometrial stromal cells were collected from patients with endometriosis and healthy controls, and the proliferation, apoptosis and migration of ectopic endometrial stromal cells transfected with ubiquitin-specific protease 10 (USP10)-siRNA or pLVX-Puro-USP10 with or without MEK inhibitor PD98059 or exogenous signaling stimulation such as epidermal growth factor (EGF) were measured by CCK-8, flow cytometry and Transwell, respectively...
October 3, 2018: American Journal of Physiology. Cell Physiology
Irena A Rebalka, Cynthia M F Monaco, Nina E Varah, Thorsten Berger, Donna M D'souza, Sarah Zhou, Tak W Mak, Thomas J Hawke
Lipocalin-2 (LCN2) is an adipokine previously described for its contribution to numerous processes including innate immunity and energy metabolism. LCN2 has also been demonstrated to be an extracellular matrix (ECM) regulator through its association with the ECM protease matrix metalloproteinase-9 (MMP-9). With the global rise in obesity and the associated co-morbidities related to increasing adiposity, it is imperative to gain an understanding of the cross-talk between adipose tissue and other metabolic tissues, such as skeletal muscle...
September 26, 2018: American Journal of Physiology. Cell Physiology
Zhaoyu Li, Szymon Wiernek, Cam Patterson, Huanchen Wang, Guoxian Qi, Xuming Dai
BACKGROUND: Hyperphosphatemia, elevated level of inorganic phosphate (Pi) in serum, is associated with increased cardiovascular morbidities and mortality. The effects of high Pi on endothelial cells are not well studied. This study investigated high Pi-induced endothelial cell apoptosis and the role of microRNA-21. METHODS: Mouse myocardial endothelial cells (MEC) were cultured in normal (1 mM) and high (5 mM) Pi conditions. Apoptosis was detected by TUNEL staining and flow cytometry...
September 26, 2018: American Journal of Physiology. Cell Physiology
Eamonn Bradley, Roddy J Large, Viktoriia Volodymyrivna Bihun, Nicolas D Mullins, Gerard P Sergeant, Mark A Hollywood, Keith D Thornbury
Airway smooth muscle expresses abundant BKCa channels, but their role in regulating contractions remains controversial. This study examines the effects of two potent BKCa channel openers on agonist-induced phasic contractions in rabbit and mouse bronchi. First, we demonstrated the ability of 10 μM GoSlo-SR5-130 to activate BKCa channels in inside-out patches from rabbit bronchial myocytes, where it shifted the activation V1/2 by -88 ± 11 mV (100 nM Ca2+ , n=7). In mouse airway smooth muscle cells, GoSlo-SR5-130 dose-dependently shifted V1/2 by 12-83 mV over a concentration range of 1-30 μM...
September 26, 2018: American Journal of Physiology. Cell Physiology
Aytan Musayeva, Caroline Manicam, Andreas Steege, Christoph Brochhausen, Beate K Straub, Katharina Bell, Norbert Pfeiffer, Adrian Gericke
Adrenergic stimuli are important for corneal epithelial structure and healing. The purpose of the present study was to examine the hypothesis that the lack of a single α1 -adrenoceptor (α1 -AR) subtype affects corneal epithelial thickness and cell proliferation. Expression levels of α1 -AR mRNA were determined in mouse cornea using real-time PCR. In mice devoid of one of the three α1-AR subtypes (α1A -AR-/- , α1B -AR-/- , α1D -AR-/- ) and in wild-type controls, thickness of individual corneal layers, the amount of epithelial cell layers and average epithelial cell size were determined in cryosections...
September 26, 2018: American Journal of Physiology. Cell Physiology
Takashi Ashino, Takashi Kohno, Varadarajan Sudhahar, Dipankar Ash, Masuko Ushio-Fukai, Tohru Fukai
Vascular smooth muscle cell (VSMC) migration contributes to neointimal formation after vascular injury. We previously demonstrated that copper (Cu) transporter ATP7A is involved in PDGF-induced VSMC migration in Cu- and Rac1-dependent manner. Underlying mechanism is still unknown. Here we show that ATP7A interacts with IQGAP1, a Rac1- and receptor tyrosine kinase-binding scaffold proteins, which mediates PDGF-induced VSMC migration and vascular remodeling. In cultured rat aortic SMCs, PDGF stimulation rapidly promoted ATP7A association with IQGAP1 and Rac1, and their translocation to lipid rafts and leading edge...
September 26, 2018: American Journal of Physiology. Cell Physiology
Klemen Dolinar, Vid Jan, Mojca Pavlin, Alexander V Chibalin, Sergej Pirkmajer
AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an adenosine analogue, is a standard positive control for AMPK activation in cell-based assays. Some broadly used cell culture media, such as MEMα, contain high concentrations of adenosine and other nucleosides. We determined whether such media alter AICAR action in skeletal muscle and cancer cells...
September 19, 2018: American Journal of Physiology. Cell Physiology
Yong-Bing Wang, Quan Shi, Gang Li, Jun-Hua Zheng, Jie Lin, Wei Qiu
Colorectal cancer (CRC) affects people globally and lymph node metastasis (LNM) is an important indicator of poor clinical outcome in CRC. The current study aims to evaluate the role of microRNA-448 (miR-488) and claudin-2 (CLDN2) in epithelial-mesenchymal transition (EMT) and LNM of CRC through the MAPK signaling pathway. Firstly, microarray analysis indicated that MiR-488 was poorly expressed in CRC, whereas CLDN2 was highly expressed. Additionally, the bioinformatics website, and the dual luciferase reporter gene assay found that CLDN2 was a target gene of miR-488...
September 12, 2018: American Journal of Physiology. Cell Physiology
Blas A Guigni, Damien M Callahan, Timothy W Tourville, Mark S Miller, Brad Fiske, Thomas Voigt, Bethany Korwin-Mihavics, Vikas Anathy, Kim Dittus, Michael J Toth
How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women diagnosed with breast cancer, who were receiving adjuvant chemotherapy following tumor resection, and 12 non-diseased controls. Breast cancer patients showed reduced single muscle fiber cross-sectional area (CSA) and fractional content of both sub-sarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss and increased reactive oxygen species (ROS) production in C2C12 muscle myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes...
September 12, 2018: American Journal of Physiology. Cell Physiology
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