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Progranulin

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https://www.readbyqxmd.com/read/28433812/the-perlecan-interacting-growth-factor-progranulin-regulates-ubiquitination-sorting-and-lysosomal-degradation-of-sortilin
#1
Ryuta Tanimoto, Chiara Palladino, Shi-Qiong Xu, Simone Buraschi, Thomas Neill, Leonard G Gomella, Stephen C Peiper, Antonino Belfiore, Renato V Iozzo, Andrea Morrione
Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression...
April 20, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28415822/interaction-between-granulin-a-and-enolase-1-attenuates-the-migration-and-invasion-of-human-hepatoma-cells
#2
Xiaoliang Chen, Huanli Xu, Ning Wu, Xiujun Liu, Gan Qiao, Shuonan Su, Ye Tian, Ru Yuan, Cong Li, Xiaohui Liu, Xiukun Lin
Granulin A (GRN A), a peptide with a molecular 6 kDa, is derived from proteolysis of progranulin (PGRN). Previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly. In the present study, we confirmed that GRN A can bind to α-enolase (ENO1) specifically as analyzed using Pull-down/MS approaches. The interaction of GRN A with ENO1 was further confirmed by Western blotting and Surface plasmon resonance (SPR) analysis. Treatment of human HepG-2 cells with GRN A inhibited cancer cell growth as well as migration and invasion of cancer cells as analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) and Scratch wound healing assay as well as Transwell experiments...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412748/tumor-necrosis-factor-receptor-2-akt-and-erk-signaling-pathways-contribute-to-the-switch-from-fibroblasts-to-cafs-by-progranulin-in-microenvironment-of-colorectal-cancer
#3
Linlin Wang, Dong Yang, Jing Tian, Aiqin Gao, Yihang Shen, Xia Ren, Xia Li, Guosheng Jiang, Taotao Dong
Cancer associated fibroblasts (CAFs) are a crucial cellular component in tumor microenvironment and could promote tumor progression. CAFs are usually derived from resident fibroblasts, which undergoing an activated process stimulated by tumor cells. However, the agents and mechanism driving this switch have not yet been elucidated. Progranulin (PGRN), a well acknowledged secreted glycoprotein, could promote proliferation and angiogenesis of colorectal cancer (CRC) cells, and high expression of PGRN correlated with patient poor prognosis...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404863/individuals-with-progranulin-haploinsufficiency-exhibit-features-of-neuronal-ceroid-lipofuscinosis
#4
Michael E Ward, Robert Chen, Hsin-Yi Huang, Connor Ludwig, Maria Telpoukhovskaia, Ali Taubes, Helene Boudin, Sakura S Minami, Meredith Reichert, Philipp Albrecht, Jeffrey M Gelfand, Andres Cruz-Herranz, Christian Cordano, Marcel V Alavi, Shannon Leslie, William W Seeley, Bruce L Miller, Eileen Bigio, Marek-Marsel Mesulam, Matthew S Bogyo, Ian R Mackenzie, John F Staropoli, Susan L Cotman, Eric J Huang, Li Gan, Ari J Green
Heterozygous mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal dementia (FTD), a neurodegenerative syndrome of older adults. Homozygous GRN mutations, on the other hand, lead to complete PGRN loss and cause neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease usually seen in children. Given that the predominant clinical and pathological features of FTD and NCL are distinct, it is controversial whether the disease mechanisms associated with complete and partial PGRN loss are similar or distinct...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28380680/progranulin-regulates-neurogenesis-in-the-developing-vertebrate-retina
#5
Caroline E Walsh, Peter F Hitchcock
We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed - retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina...
April 5, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28379303/restoring-neuronal-progranulin-reverses-deficits-in-a-mouse-model-of-frontotemporal-dementia
#6
Andrew E Arrant, Anthony J Filiano, Daniel E Unger, Allen H Young, Erik D Roberson
Loss-of-function mutations in progranulin (GRN), a secreted glycoprotein expressed by neurons and microglia, are a common autosomal dominant cause of frontotemporal dementia, a neurodegenerative disease commonly characterized by disrupted social and emotional behaviour. GRN mutations are thought to cause frontotemporal dementia through progranulin haploinsufficiency, therefore, boosting progranulin expression from the intact allele is a rational treatment strategy. However, this approach has not been tested in an animal model of frontotemporal dementia and it is unclear if boosting progranulin could correct pre-existing deficits...
March 29, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28358904/neurotrophic-effects-of-progranulin-in-vivo-in-reversing-motor-neuron-defects-caused-by-over-or-under-expression-of-tdp-43-or-fus
#7
Babykumari P Chitramuthu, Denis G Kay, Andrew Bateman, Hugh P J Bennett
Progranulin (PGRN) is a glycoprotein with multiple roles in normal and disease states. Mutations within the GRN gene cause frontotemporal lobar degeneration (FTLD). The affected neurons display distinctive TAR DNA binding protein 43 (TDP-43) inclusions. How partial loss of PGRN causes TDP-43 neuropathology is poorly understood. TDP-43 inclusions are also found in affected neurons of patients with other neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. In ALS, TDP-43 inclusions are typically also immunoreactive for fused in sarcoma (FUS)...
2017: PloS One
https://www.readbyqxmd.com/read/28304311/frontotemporal-dementia-due-to-the-novel-grn-arg161glyfsx36-mutation
#8
Stefano Gazzina, Silvana Archetti, Antonella Alberici, Elisa Bonomi, Maura Cosseddu, Diego Di Lorenzo, Alessandro Padovani, Barbara Borroni
Progranulin is a multifunctional growth factor mainly expressed in neurons and microglia. Loss-of-function mutations in the Granulin (GRN) gene are causative of frontotemporal dementia with TAR DNA-binding protein-43 inclusions. We reported the case of a 51-year-old male patient affected by sporadic agrammatic variant of primary progressive aphasia, in whom we identified a novel heterozygous deletion in the exon 6 (g.10338_39delAG, p.Arg161GlyfsX36). Plasma progranulin levels were significantly reduced and in silico analysis predicted a premature termination codon...
March 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28300056/imbalance-between-tnf%C3%AE-and-progranulin-contributes-to-memory-impairment-and-anxiety-in-sleep-deprived-mice
#9
Kun Zhang, Yu-Jiao Li, Dan Feng, Peng Zhang, Ya-Tao Wang, Xiang Li, Shui-Bing Liu, Yu-Mei Wu, Ming-Gao Zhao
Sleep disorder is becoming a widespread problem in current society, and is associated with impaired cognition and emotional disorders. Progranulin (PGRN), also known as granulin epithelin precursor, promotes neurite outgrowth and cell survival, and is encoded by the GRN gene. It is a tumor necrosis factor α receptor (TNFR) ligand which is implicated in many central nervous system diseases. However, the role PGRN in sleep disorder remains unclear. In the present study, we found that sleep deprivation (S-DEP) impaired the memory and produced thigmotaxis/anxiety-like behaviors in mice...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293019/novel-adipokines-methodological-utility-in-human-obesity-research
#10
F Eichelmann, N Rudovich, A F Pfeiffer, M B Schulze, R di Giuseppe, H Boeing, K Aleksandrova
BACKGROUND: Adipokines could pose a link between adiposity, systemic inflammation and metabolic disease risk. However, it is unclear whether representative biomarkers are methodologically suitable for use in human obesity research. METHODS: We assessed the intra-individual reproducibility of selected adipokines in a sample of 207 apparently healthy participants with available biosample collections over 4 month period. Concentrations of the following adipokines were measured at each sampling time point: fatty-acid binding protein-4 (FABP-4), lipocalin-2, monocyte chemoattractant protein 1 (MCP-1), procalcitonin, progranulin, vaspin and visfatin/Nampt...
March 15, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28285794/missense-mutation-in-grn-gene-affecting-rna-splicing-and-plasma-progranulin-level-in-a-family-affected-by-frontotemporal-lobar-degeneration
#11
Simona Luzzi, Lara Colleoni, Paola Corbetta, Sara Baldinelli, Chiara Fiori, Francesca Girelli, Mauro Silvestrini, Paola Caroppo, Giorgio Giaccone, Fabrizio Tagliavini, Giacomina Rossi
Gene coding for progranulin, GRN, is a major gene linked to frontotemporal lobar degeneration. While most of pathogenic GRN mutations are null mutations leading to haploinsufficiency, GRN missense mutations do not have an obvious pathogenicity, and only a few have been revealed to act through different pathogenetic mechanisms, such as cytoplasmic missorting, protein degradation, and abnormal cleavage by elastase. The aim of this study was to disclose the pathogenetic mechanisms of the GRN A199V missense mutation, which was previously reported not to alter physiological progranulin features but was associated with a reduced plasma progranulin level...
February 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28273689/progranulin-protects-lung-epithelial-cells-from-cigarette-smoking-induced-apoptosis
#12
Kyoung Young Lee, So-Young Park, Sunjoo Park, Gyong Hwa Hong, Keun-Ai Moon, You-Sun Kim, Yeon-Mok Oh, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho
BACKGROUND AND OBJECTIVE: Emphysema is characterized by irreversible destruction of alveolar walls with distal air space enlargement. Cigarette smoke (CS) is considered a major risk factor for emphysematous changes in COPD. Progranulin (PGRN), a glycoprotein induced by CS, has been reported to participate in apoptosis. However, the precise role of PGRN in emphysema is currently unknown. This study aimed to evaluate the role of PGRN in human alveolar epithelial cells (AECs) in response to CS...
March 8, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28268100/intrafamilial-variable-phenotype-including-corticobasal-syndrome-in-a-family-with-p-p301l-mutation-in-the-mapt-gene-first-report-in-south-america
#13
Emilia M Gatto, Ricardo F Allegri, Gustavo Da Prat, Patricio Chrem Mendez, David S Hanna, Michael O Dorschner, Ezequiel I Surace, Cyrus P Zabetian, Ignacio F Mata
Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and also in the genes coding for the protein associated with microtubule tau (MAPT) and progranulin (GRN) on chromosome 17 (FTDP-17). Herein, we report an Argentinean family, of Basque ancestry, with an extensive family history of behavioral variant of FTD...
May 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28247166/progranulin-protects-against-osteonecrosis-of-the-femoral-head-by-activating-erk1-2-pathway
#14
Yingguang Han, Meng Si, Yunpeng Zhao, Yi Liu, Kaiyuan Cheng, Yuedong Zhang, Jialin Jia, Jingkun Li, Lin Nie
The aim of this study was to investigate progranulin (PGRN) expression and its effect in cartilage degradation and in the pathogenesis of osteonecrosis of the femoral head (ONFH). Cartilage specimens were obtained from ONFH and FNF patients and PGRN expression was analyzed by immunohistochemistry, western blot analysis, and RT-PCR. Peripheral blood PGRN level was detected by ELISA. Additionally, primary chondrocytes were cultured and treated with PGRN. Next, the expression of aggrecan and collagen II and the activation of ERK1/2 were detected...
February 28, 2017: Inflammation
https://www.readbyqxmd.com/read/28245590/progranulin-and-its-related-micrornas-after-status-epilepticus-possible-mechanisms-of-neuroprotection
#15
REVIEW
Peter Körtvelyessy, Tessa Huchtemann, Hans-Jochen Heinze, Daniel M Bittner
The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28225367/progranulin-gene-variation-affects-serum-progranulin-levels-differently-in-danish-bipolar-individuals-compared-with-healthy-controls
#16
Henriette N Buttenschøn, Marit N Nielsen, Gangadaar Thotakura, Chris W Lee, Anders Nykjær, Ole Mors, Simon Glerup
OBJECTIVES: The identification of peripheral biomarkers for bipolar disorder is of great importance and has the potential to improve diagnosis, treatment and prognosis. Recent studies have reported lower plasma progranulin levels in bipolar individuals compared with controls and association with single nucleotide polymorphisms (SNPs) within the progranulin gene (GRN). In the present study, we investigated the effect of GRN and sortilin (SORT1) gene variation on serum progranulin levels in bipolar individuals and controls...
February 20, 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/28194047/progranulin-inhibits-human-t-lymphocyte-proliferation-by-inducing-the-formation-of-regulatory-t-lymphocytes
#17
Kyu Hwan Kwack, Hyeon-Woo Lee
We have examined the effect of progranulin (PGRN) on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28174682/glucose-deprivation-regulates-the-progranulin-sortilin-axis-in-pc12-cells
#18
Ken-Ichi Kawashima, Yuri Ishiuchi, Miki Konnai, Saori Komatsu, Hitoshi Sato, Hideo Kawaguchi, Nobumitsu Miyanishi, Jérôme Lamartine, Masugi Nishihara, Taku Nedachi
Progranulin (PGRN) is a growth factor implicated in several neurodegenerative diseases, such as frontotemporal lobar degeneration. Despite its important role in the central nervous system (CNS), the mechanisms controlling PGRN expression in the CNS are largely unknown. Recent evidence, however, suggested that several stressors, such as hypoxia, acidosis, or oxidative stress, induce PGRN expression. The present study was mainly aimed at determining whether and, if so, how glucose deprivation affects PGRN expression in PC12 cells...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28153380/grn-deletion-in-familial-frontotemporal-dementia-showing-association-with-clinical-variability-in-3-familial-cases
#19
Graziella Milan, Sabrina Napoletano, Sabina Pappatà, Maria Teresa Gentile, Luca Colucci-D'Amato, Gennaro Della Rocca, Anna Maciag, Carmen Palermo Rossetti, Laura Fucci, Annibale Puca, Dario Grossi, Alfredo Postiglione, Emilia Vitale
Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We present evidence that all the available patients in these 3 familial cases are carrying the rare GRN gene exon 6 deletion g10325_10331delCTGCTGT (relative to nt 1 inNG_007886...
May 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28143512/progranulin-causes-adipose-insulin-resistance-via-increased-autophagy-resulting-from-activated-oxidative-stress-and-endoplasmic-reticulum-stress
#20
Qinyue Guo, Lin Xu, Huixia Li, Hongzhi Sun, Jiali Liu, Shufang Wu, Bo Zhou
BACKGROUND: Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. METHODS: In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed...
January 31, 2017: Lipids in Health and Disease
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