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Progranulin

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https://www.readbyqxmd.com/read/29452214/pgrn-promotes-lymphangiogenesis-through-vegf-c-and-is-an-independent-risk-factor-in-human-esophageal-cancers
#1
Guanhua Li, Taotao Dong, Dong Yang, Aiqin Gao, Judong Luo, Hongyan Yang, Linlin Wang
Lymph node metastasis is one of the most important predictor of the prognosis for esophageal cancer (EC) patients. Yet, the mechanism underlying the lymph node metastasis is largely unknown. Progranulin (PGRN) is shown to be highly expressed in various types of cancers and could promote the angiogenesis and epithelial mesenchymal transition (EMT) of cancer cells in previous studies. However, the expression status of PGRN and its effects on the lymphangiogenesis in EC is largely unclear. In this study, we show for the first time that PGRN is expressed in EC tissue samples and cell lines and could promote the expression of VEGF-C in vitro, a well-known lymphangiogenesis inducer, through the putative signaling transducers p-ERK and p-AKT...
February 13, 2018: Human Pathology
https://www.readbyqxmd.com/read/29434051/downregulation-of-exosomal-mir-204-5p-and-mir-632-as-a-biomarker-for-ftd-a-genfi-study
#2
Raphael Schneider, Paul McKeever, TaeHyung Kim, Caroline Graff, John Cornelis van Swieten, Anna Karydas, Adam Boxer, Howie Rosen, Bruce L Miller, Robert Laforce, Daniela Galimberti, Mario Masellis, Barbara Borroni, Zhaolei Zhang, Lorne Zinman, Jonathan Daniel Rohrer, Maria Carmela Tartaglia, Janice Robertson
OBJECTIVE: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. METHODS: GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier...
February 6, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29408220/a-potent-tilapia-secreted-granulin-peptide-enhances-the-survival-of-transgenic-zebrafish-infected-by-vibrio-vulnificus-via-modulation-of-innate-immunity
#3
Sheng-Han Wu, Hong-Jie Lin, Wen-Fu Lin, Jen-Leih Wu, Hong-Yi Gong
Progranulin (PGRN) is a multi-functional growth factor that mediates cell proliferation, survival, migration, tumorigenesis, wound healing, development, and anti-inflammation activity. A novel alternatively spliced transcript from the short-form PGRN1 gene encoding a novel, secreted GRN peptide composed of 20-a.a. signal peptide and 41-a.a. GRN named GRN-41 was identified to be abundantly expressed in immune-related organs including spleen, head kidney, and intestine of Mozambique tilapia. The expression of GRN-41 and PGRN1 were further induced in the spleen of tilapia challenged with Vibrio vulnificus at 3 h post infection (hpi) and 6 hpi, respectively...
February 2, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29403285/progranulin-modulates-cholangiocarcinoma-cell-proliferation-apoptosis-and-motility-via-the-pi3k-pakt-pathway
#4
Minerva Daya, Watcharin Loilome, Anchalee Techasen, Malinee Thanee, Prakasit Sa-Ngiamwibool, Attapol Titapun, Puangrat Yongvanit, Nisana Namwat
Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29398357/retrograde-signaling-from-progranulin-to-sort1-counteracts-synapse-elimination-in-the-developing-cerebellum
#5
Naofumi Uesaka, Manabu Abe, Kohtarou Konno, Maya Yamazaki, Kazuto Sakoori, Takaki Watanabe, Tzu-Huei Kao, Takayasu Mikuni, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16...
January 26, 2018: Neuron
https://www.readbyqxmd.com/read/29396296/chitinase-3-like-protein-1-a-progranulin-downstream-molecule-and-potential-biomarker-for-gaucher-disease
#6
Jinlong Jian, Yuehong Chen, Rossella Liberti, Wenyu Fu, Wenhuo Hu, Rachel Saunders-Pullman, Gregory M Pastores, Ying Chen, Ying Sun, Gregory A Grabowski, Chuan-Ju Liu
We recently reported that progranulin (PGRN) is a novel regulator of glucocerebrosidase and its deficiency associates with Gaucher Diseases (GD) (Jian et al., 2016a; Jian et al., 2018). To isolate the relevant downstream molecules, we performed a whole genome microarray and mass spectrometry analysis, which led to the isolation of Chitinase-3-like-1 (CHI3L1) as one of the up-regulated genes in PGRN null mice. Elevated levels of CHI3L1 were confirmed by immunoblotting and immunohistochemistry. In contrast, treatment with recombinant Pcgin, a derivative of PGRN, as well as imigluerase, significantly reduced the expressions of CHI3L1 in both PGRN null GD model and the fibroblasts from GD patients...
January 30, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29382817/targeting-tyro3-ameliorates-a-model-of-pgrn-mutant-ftld-tdp-via-tau-mediated-synaptic-pathology
#7
Kyota Fujita, Xigui Chen, Hidenori Homma, Kazuhiko Tagawa, Mutsuki Amano, Ayumu Saito, Seiya Imoto, Hiroyasu Akatsu, Yoshio Hashizume, Kozo Kaibuchi, Satoru Miyano, Hitoshi Okazawa
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI). Phosphoproteomic analysis of this model revealed activation of signaling pathways connecting PKC and MAPK to tau prior to TDP43 aggregation and cognitive impairments, and identified PKCα as the kinase responsible for the early-stage tau phosphorylation at Ser203. Disinhibition of Gas6 binding to Tyro3 due to PGRN reduction results in activation of PKCα via PLCγ, inducing tau phosphorylation at Ser203, mislocalization of tau to dendritic spines, and spine loss...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29378861/progranulin-gene-therapy-improves-lysosomal-dysfunction-and-microglial-pathology-associated-with-frontotemporal-dementia-and-neuronal-ceroid-lipofuscinosis
#8
Andrew E Arrant, Vincent C Onyilo, Daniel E Unger, Erik D Roberson
Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV-Grn) to deliver progranulin in Grn-/- mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis...
January 29, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29370838/extended-ftld-pedigree-segregating-a-belgian-grn-null-mutation-neuropathological-heterogeneity-in-one-family
#9
Anne Sieben, Sara Van Mossevelde, Eline Wauters, Sebastiaan Engelborghs, Julie van der Zee, Tim Van Langenhove, Patrick Santens, Marleen Praet, Paul Boon, Marijke Miatton, Sofie Van Hoecke, Mathieu Vandenbulcke, Rik Vandenberghe, Patrick Cras, Marc Cruts, Peter Paul De Deyn, Christine Van Broeckhoven, Jean-Jacques Martin
BACKGROUND: In this paper, we describe the clinical and neuropathological findings of nine members of the Belgian progranulin gene (GRN) founder family. In this family, the loss-of-function mutation IVS1 + 5G > C was identified in 2006. In 2007, a clinical description of the mutation carriers was published that revealed the clinical heterogeneity among IVS1 + 5G > C carriers. We report our comparison of our data with the published clinical and neuropathological characteristics of other GRN mutations as well as other frontotemporal lobar degeneration (FTLD) syndromes, and we present a review of the literature...
January 22, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29365585/progranulin-attenuates-in-vivo-acute-myocardial-ischemia-reperfusion-injury-in-a-rat-model-of-hypercholesterolemia
#10
Asma Mohammed Alyahya, Abeer Al Masri, Eman Eleter, Ahmed Alhersi
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29340960/higher-levels-of-progranulin-in-cerebrospinal-fluid-of-patients-with-lymphoma-and-carcinoma-with-cns-metastasis
#11
Akio Kimura, Masao Takemura, Ginette Serrero, Nobuaki Yoshikura, Yuichi Hayashi, Kuniaki Saito, Takashi Inuzuka
Assessing central nervous system (CNS) involvement in patients with lymphoma or carcinoma is important in determining therapy and prognosis. Progranulin (PGRN) is a secreted glycosylated protein with roles in cancer growth and survival; it is highly expressed in aggressive cancer cell lines and specimens from many cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma [12 with CNS metastasis (CNS+); 6 without CNS metastasis (CNS-)], 21 with carcinomas (10 CNS+; 11 CNS-), and 191 control patients with non-cancer neurological diseases, and compared PRGN levels among these disease groups...
January 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29325128/relationship-between-twelve-adipocytokines-and-distinct-components-of-the-metabolic-syndrome
#12
Thomas Ebert, Claudia Gebhardt, Markus Scholz, Tobias Wohland, Dorit Schleinitz, Mathias Fasshauer, Matthias Blüher, Michael Stumvoll, Peter Kovacs, Anke Tönjes
Objective: Adipose tissue-derived signals potentially link obesity and adipose tissue dysfunction with metabolic and cardiovascular diseases. Although some adipocytokines have been closely related to metabolic and cardiovascular traits, it remains open which adipocytokine or adipocytokine cluster serve as meaningful marker of metabolic syndrome (MS) components. Therefore, this study investigates the associations of twelve adipocytokines with components of the MS to identify the most relevant cytokines potentially related to specific metabolic profiles...
January 9, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29323121/the-endogenous-grp78-interactome-in-human-head-and-neck-cancers-a-deterministic-role-of-cell-surface-grp78-in-cancer-stemness
#13
Hsin-Ying Chen, Joseph Tung-Chieh Chang, Kun-Yi Chien, Yun-Shien Lee, Guo-Rung You, Ann-Joy Cheng
Cell surface glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, was suggested to be a cancer stem cell marker, but the influence of this molecule on cancer stemness is poorly characterized. In this study, we developed a mass spectrometry platform to detect the endogenous interactome of GRP78 and investigated its role in cancer stemness. The interactome results showed that cell surface GRP78 associates with multiple molecules. The influence of cell population heterogeneity of head and neck cancer cell lines (OECM1, FaDu, and BM2) according to the cell surface expression levels of GRP78 and the GRP78 interactome protein, Progranulin, was investigated...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312639/progranulin-derived-engineered-protein-atsttrin-suppresses-tnf-%C3%AE-mediated-inflammation-in-intervertebral-disc-degenerative-disease
#14
Hong Ding, Jianlu Wei, Yunpeng Zhao, Yi Liu, Lian Liu, Lei Cheng
Atsttrin, an engineered molecule composed of three fragments of progranulin(PGRN), exerts comparable anti-inflammation ability. Intervertebral disc degeneration (IDD) is involved in inflammation in which TNF-α plays a key role. This study aims to examine the effect and the mechanism of Atsttrin in the pathogenesis of intervertebral disc degeneration. For this purpose, we took advantage of murine and human intervertebral disc (IVD) and examined the expression of TNF-α in IVD tissues using immunohistochemistry and TNF-α level in peripheral sera by ELISA assay...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29258611/progranulin-derivative-atsttrin-protects-against-early-osteoarthritis-in-mouse-and-rat-models
#15
Jian-Lu Wei, Wenyu Fu, Yuan-Jing Ding, Aubryanna Hettinghouse, Matin Lendhey, Ran Schwarzkopf, Oran D Kennedy, Chuan-Ju Liu
BACKGROUND: Atsttrin, an engineered protein composed of three tumor necrosis factor receptor (TNFR)-binding fragments of progranulin (PGRN), shows therapeutic effect in multiple murine models of inflammatory arthritis . Additionally, intra-articular delivery of PGRN protects against osteoarthritis (OA) progression. The purpose of this study is to determine whether Atsttrin also has therapeutic effects in OA and the molecular mechanisms involved. METHODS: Surgically induced and noninvasive rupture OA models were established in mouse and rat, respectively...
December 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29249935/loss-of-neuroprotective-factors-in-neurodegenerative-dementias-the-end-or-the-starting-point
#16
REVIEW
Luisa Benussi, Giuliano Binetti, Roberta Ghidoni
Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). We will report evidences that the Brain Derived Neurotrophic Factor (BDNF), the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29249750/progranulin-deficiency-leads-to-prolonged-persistence-of-macrophages-accompanied-with-myofiber-hypertrophy-in-regenerating-muscle
#17
Hidetoshi Sugihara, Kei Miyaji, Keitaro Yamanouchi, Takashi Matsuwaki, Masugi Nishihara
Skeletal muscle has an ability to regenerate in response to injury due to the presence of satellite cells. Injury in skeletal muscle causes infiltration of pro-inflammatory macrophages (M1 macrophages) to remove necrotic myofibers, followed by their differentiation into anti-inflammatory macrophages (M2 macrophages) to terminate the inflammation. Since both M1 and M2 macrophages play important roles, coordinated regulation of their kinetics is important to complete muscle regeneration successfully. Progranulin (PGRN) is a pluripotent growth factor, having a protective role against the inflamed tissue...
December 18, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29226876/serum-c-peptide-visfatin-resistin-and-ghrelin-are-altered-in-sporadic-and-grn-associated-frontotemporal-lobar-degeneration
#18
Roberta Zanardini, Luisa Benussi, Silvia Fostinelli, Claudia Saraceno, Miriam Ciani, Barbara Borroni, Alessandro Padovani, Giuliano Binetti, Roberta Ghidoni
Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative disease characterized by progressive deterioration of the frontal and anterior temporal lobes of the brain resulting in different heterogeneous conditions, mainly characterized by personality changes, behavioral disturbances, such as binge eating, and deficits in language and executive functions. Null mutations in progranulin gene (GRN) are one of the most frequent genetic determinants in familial frontotemporal dementia. Recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance revealing its metabolic function...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29186428/genome-wide-meta-analysis-identifies-novel-determinants-of-circulating-serum-progranulin
#19
Anke Tönjes, Markus Scholz, Jacqueline Krüger, Kerstin Krause, Dorit Schleinitz, Holger Kirsten, Claudia Gebhardt, Carola Marzi, Harald Grallert, Claes Ladenvall, Henrike Heyne, Esa Laurila, Jennifer Kriebel, Christa Meisinger, Wolfgang Rathmann, Christian Gieger, Leif Groop, Inga Prokopenko, Bo Isomaa, Frank Beutner, Jürgen Kratzsch, Antje Fischer-Rosinsky, Andreas Pfeiffer, Knut Krohn, Joachim Spranger, Joachim Thiery, Matthias Blüher, Michael Stumvoll, Peter Kovacs
Progranulin is a secreted protein with important functions in processes including immune and inflammatory response, metabolism and embryonic development. The present study aimed at identification of genetic factors determining progranulin concentrations.We conducted a genome-wide association meta-analysis for serum progranulin in three independent cohorts from Europe: Sorbs (N = 848) and KORA (N = 1,628) from Germany and PPP-Botnia (N = 335) from Finland (total N = 2,811). SNPs associated with progranulin levels were replicated in two additional German cohorts: LIFE Heart Study (Leipzig; N = 967) and Metabolic Syndrome Berlin Potsdam (Berlin cohort; N = 833)...
November 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29176029/serum-progranulin-levels-in-relation-to-insulin-resistance-in-childhood-obesity
#20
Eman M Alissa, Rima H Sutaih, Hayat Z Kamfar, Abdulmoeen E Alagha, Zuhair M Marzouki
BACKGROUND: Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. METHODS: A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia...
November 27, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
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