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Min Zhao, Wankun Xie, Shu-Huai Tsai, Travis W Hein, Brent A Rocke, Lih Kuo, Robert H Rosa
Purpose: The purpose of this study was to investigate the impact of stanniocalcin-1 (STC-1), a photoreceptor-protective glycoprotein, on the development of choroidal neovascularization (CNV) in relation to VEGF and its main receptor (VEGFR2) expression after laser injury. Methods: In rats, CNV was induced by laser photocoagulation in both eyes, followed by intravitreal injection of STC-1 in the right eye and vehicle or denatured STC-1 injection in the left eye as control...
February 1, 2018: Investigative Ophthalmology & Visual Science
Cherry Ct Leung, Chris Kc Wong
Stanniocalcin-1 (STC1) is a paracrine factor associated with inflammation and carcinogenesis. Using clinicopathological data, we previously reported that a greater expression of STC1 in hepatocellular carcinoma (HCC) was significantly correlated with smaller tumor size. The underlying mechanism on the correlation is not known. In this study, using a metastatic HCC cell-line (MHCC-97L, P) and lentiviral vector mediated-STC1 overexpression, the inoculation of STC1-overexpressing MHCC-97L (S1) cells in a nude mice xenograft model demonstrated reductions in tumor mass and volume...
January 23, 2018: Oncotarget
Kapka Miteva, Kathleen Pappritz, Marzena Sosnowski, Muhammad El-Shafeey, Irene Müller, Fengquan Dong, Konstantinos Savvatis, Jochen Ringe, Carsten Tschöpe, Sophie Van Linthout
Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice...
February 12, 2018: Scientific Reports
Rikke Hjortebjerg, Darlene E Berryman, Ross Comisford, Edward O List, Claus Oxvig, Mette Bjerre, Jan Frystyk, John J Kopchick
INTRODUCTION: Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF)-I action through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. Most members of the IGF system are expressed in adipose tissue (AT), but there is a relative paucity of information on the distribution of IGFBP-4, PAPP-A, and STC2 in different AT depots. Since IGF-I expression in AT is highly GH-dependent, we used bovine GH transgenic (bGH) and GH receptor knockout (GHR-/-) mice to investigate AT depot-specific expression patterns of IGFBP-4, PAPP-A, and STC2, and whether the regulation is GH-dependent...
February 2, 2018: Growth Hormone & IGF Research
Masanobu Fujimoto, Vivian Hwa, Andrew Dauber
Growth hormone (GH) and its mediator, insulin-like growth factor-1 (IGF-1), play a critical role in human growth. In circulation, IGF-1 is found in a ternary complex with IGF binding proteins (IGFBPs) and acid labile subunit (ALS) but little attention has been paid to the regulation of IGF-1 bioavailability. Recently, pregnancy-associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) were identified as novel modulators of IGF-I bioavailability. PAPP-A2 is a protease which cleaves IGFBP-3 and -5, while STC2 inhibits PAPP-A and PAPP-A2 activity...
December 30, 2017: Journal of Clinical Research in Pediatric Endocrinology
Hongwei Cheng, Zhixian Wu, Caisheng Wu, Xiaoyuan Wang, Sing Shy Liow, Zibiao Li, Yun-Long Wu
Stanniocalcin 2 (STC2) overexpression in hepatocellular carcinoma (HCC) could lead to poor prognosis, which might be due to its induced P-glycoprotein and Bcl-2 protein expression level increase. P-glycoprotein or membrane pump induced drug efflux and altered prosurvival Bcl-2 expression are key mechanisms for drug resistance leading to failure of chemotherapy in HCC. However, current strategy to overcome both P-glycoprotein and Bcl-2 protein induced drug resistance was rarely reported. In this work, we utilized an amphiphilic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) cationic polyester to encapsulate chemotherapeutic paclitaxel (PTX) in hydrophobic PHB domain and Bcl-2 convertor Nur77/ΔDBD gene (Nur77 without DNA binding domain for mitochondria localization) by formation of polyplex due to cationic PDMAEMA segment, to effectively inhibit the drug resistant HepG2/STC2 and SMCC7721/STC2 liver cancer cell growth...
February 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Yong Li, Zhi-Cheng He, Xiao-Ning Zhang, Qing Liu, Cong Chen, Zheng Zhu, Qian Chen, Yu Shi, Xiao-Hong Yao, You-Hong Cui, Xia Zhang, Yan Wang, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Glioblastoma (GBM) is a fatal tumor and comprises heterogeneous cells in which a subpopulation with stem cell-like properties is included. Cancer cells with stem cell-like properties account for tumor initiation, drug resistance and recurrence. To identify and characterize specific factors in regulating stem-like traits is critical for GBM therapeutic. Here, we showed that Stanniocalcin-1 (STC1), a secretory glycoprotein, functions as a novel stimulator for stem-like traits of GBM cells. We found STC1 was prominently expressed in glioma spheres which are mainly comprised of glioma stem-like cells...
March 1, 2018: Cancer Letters
Lucas S Torati, Hervé Migaud, Mary K Doherty, Justyna Siwy, Willian Mullen, Pedro E C Mesquita, Amaya Albalat
Parental investment in Arapaima gigas includes nest building and guarding, followed by a care provision when a cephalic fluid is released from the parents' head to the offspring. This fluid has presumably important functions for the offspring but so far its composition has not been characterised. In this study the proteome and peptidome of the cephalic secretion was studied in parental and non-parental fish using capillary electrophoresis coupled to mass spectrometry (CE-MS) and GeLC-MS/MS analyses. Multiple comparisons revealed 28 peptides were significantly different between males and parental males (PC-males), 126 between females and parental females (PC-females), 51 between males and females and 9 between PC-males and PC-females...
2017: PloS One
José Javier López, Isaac Jardín, Carlos Cantonero Chamorro, Manuel Luis Duran, María José Tarancón Rubio, Maria Reyes Panadero, Francisca Jiménez, Rocio Montero, María José González, Manuel Martínez, María Jose Hernández, José María Brull, Antonio Jesús Corbacho, Elena Delgado, María Purificación Granados, Luis Gómez-Gordo, Juan Antonio Rosado, Pedro Cosme Redondo
Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2-/- mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP)...
January 2018: Journal of Cellular and Molecular Medicine
Gavin W Roddy, Douglas Yasumura, Michael T Matthes, Marcel V Alavi, Sanford L Boye, Robert H Rosa, Michael P Fautsch, William W Hauswirth, Matthew M LaVail
Retinal degenerations, including age-related macular degeneration and the retinitis pigmentosa family of diseases, are among the leading causes of legal blindness in the United States. We previously found that Stanniocalcin-1 (STC-1) reduced photoreceptor loss in the S334ter-3 and Royal College of Surgeons rat models of retinal degeneration. The results were attributed in part to a reduction in oxidative stress. Herein, we tested the hypothesis that long-term delivery of STC-1 would provide therapeutic rescue in more chronic models of retinal degeneration...
December 2017: Experimental Eye Research
Grigorios Panagiotou, Athanasios D Anastasilakis, Georgios Kynigopoulos, Elpida C Skouvaklidou, Zacharias G Saridakis, Jagriti Upadhyay, Eirini Pagkalidou, Aggeliki Apostolou, Thomai Karagiozoglou-Lampoudi, Christos S Mantzoros
BACKGROUND: Insulin Growth Factor Binding Protein 4 (IGFBP-4), Stanniocalcin-2 (STC-2) and Pregnancy-Associated Plasma Protein-A (PAPP-A) have a well-documented involvement in several physiological functions in humans but predictors of their circulating levels remain largely unknown. We aimed to identify anthropometric and biochemical parameters associated with circulating levels of IGFBP-4/STC-2/PAPP-A axis (ISPa) cross-sectionally and to study their day-night variation and their regulation in response to mixed meal and exercise...
October 2017: Metabolism: Clinical and Experimental
Nilani Ramshanker, Maiken Aagaard, Rikke Hjortebjerg, Thomas Schmidt Voss, Niels Møller, Jens Otto Lunde Jørgensen, Niels Jessen, Peter Bjerring, Nils Erik Magnusson, Mette Bjerre, Claus Oxvig, Jan Frystyk
Context: Short-term glucocorticoid exposure increases serum insulinlike growth factor I (IGF-I) concentrations but antagonizes IGF-I tissue signaling. The underlying mechanisms remain unknown. Objective: To identify at which levels glucocorticoid inhibits IGF-I signaling. Design and Methods: Nineteen healthy males received prednisolone (37.5 mg/d) and placebo for 5 days in a randomized, double-blinded, placebo-controlled crossover study. Serum was collected on days 1, 3, and 5, and abdominal skin suction blister fluid (SBF; ~interstitial fluid) was taken on day 5 (n = 9) together with muscle biopsy specimens (n = 19)...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
Ulrick Skipper Espelund, Mette Bjerre, Rikke Hjortebjerg, Torben Riis Rasmussen, Anders Lundby, Andreas Hoeflich, Birgitte Holst Folkersen, Claus Oxvig, Jan Frystyk
Context: Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective: To compare activity and concentrations of IGF system components in pleural fluid and blood. Design: Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
Linsen Feng, Jianhua Ma, Haiming Ji, Yichun Liu, Weixing Hu
To investigate the repression of miR-184 on Stanniocalcin-2 (STC2) and how this axis affects the propagation, invasiveness and migration ability of glioblastoma cells. RT-PCR was employed to determine the miR-184 and STC2 mRNA expression both in tissues and cells. Western blot was employed to determine the protein expression levels. The cells were transfected via lipofection. MTT, colony formation, invasion and scratch healing assays were conducted to study the propagation, invasiveness and migratory ability of glioblastoma cells, respectively...
September 8, 2017: Pathology Oncology Research: POR
Jesús Argente, Julie A Chowen, Luis A Pérez-Jurado, Jan Frystyk, Claus Oxvig
The discovery of a mutation in a specific gene can be very important for determining the pathophysiology underlying the disease of a patient and may also help to decide the best treatment protocol on an individual basis. However, sometimes the discovery of mutations in new proteins advances our comprehension in a more widespread manner. The growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is fundamental for systemic growth, but is also involved in many other important processes. Our understanding of this system in physiology and pathophysiology has advanced throughout the years with each discovery of mutations in members of this axis...
October 2017: EMBO Molecular Medicine
Aditya D Joshi, Ekram Hossain, Cornelis J Elferink
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a plethora of target genes. Historically, the AhR has been studied as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on its binding to the xenobiotic response element (XRE) in partnership with the AhR nuclear translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel AhR target gene responsive to the endogenous AhR agonist cinnabarinic acid (CA)...
September 2017: Molecular Pharmacology
Kristy Kwan-Shuen Chan, Carmen Oi-Ning Leung, Carmen Chak-Lui Wong, Daniel Wai-Hung Ho, Kenneth Siu-Ho Chok, Ching-Lung Lai, Irene Oi-Lin Ng, Regina Cheuk-Lam Lo
The hypoxic microenvironment is well-characterized in hepatocellular carcinoma (HCC). Delineation of hypoxia-responsive events is an integral part to understand the pathogenesis of HCC. We studied the functional role and clinical relevance of Stanniocalcin 1 (STC1), a hypoxia-induced molecular target, in HCC. In our clinical cohort, STC1 transcript was up-regulated in HCC tumor tissues. Moreover, STC1 protein was detected in the sera of HCC patients. A higher serum STC1 level was correlated with larger tumor size and poorer 5-year disease-free survival...
September 10, 2017: Cancer Letters
Elīna Zandberga, Pawel Zayakin, Artūrs Ābols, Dārta Pūpola, Pēteris Trapencieris, Aija Linē
Carbonic anhydrase IX (CAIX) is a pH-regulating enzyme that plays a key role in maintaining an alkaline intracellular pH under hypoxic conditions. It is overexpressed in a variety of solid cancers, including breast cancer (BC), and has been implicated in the migration, invasion and stemness of breast cancer cells. Therefore, CAIX recently emerged as a novel therapeutic target for the treatment of BC. To gain an insight into the mechanism of action of CAIX inhibitors, we investigated the impact of CAIX knock-down on the transcriptional response to hypoxia in 2 BC cell lines - MCF7 and MDA-MB-231, by performing a global gene expression analysis...
August 3, 2017: Cancer Biology & Therapy
Wenru Su, Zuohong Li, Y Jia, Yingting Zhu, Wenjia Cai, Peixing Wan, Yingying Zhang, Song Guo Zheng, Yehong Zhuo
Mesenchymal stem cells (MSCs) have been demonstrated to have promising therapeutic benefits for a variety of neurological diseases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell (RGC) survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microglial activation, partly via the action of stanniocalcin 1 (STC1)...
August 1, 2017: Journal of Molecular Cell Biology
Gavin W Roddy, Kimberly B Viker, Nelson S Winkler, Cindy K Bahler, Bradley H Holman, David Sheikh-Hamad, Uttio Roy Chowdhury, W Daniel Stamer, Michael P Fautsch
Purpose: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost. Methods: Total RNA and protein isolated from primary human Schlemm's canal cells (n = 3) treated with latanoprost (free acid; 100 nM) were processed for quantitative PCR and Western blot analysis. IOP was evaluated in stanniocalcin-1 (STC-1-/-) and wild-type mice following treatment with latanoprost or Rho kinase inhibitor Y27632...
May 1, 2017: Investigative Ophthalmology & Visual Science
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