Hypoxia induces up-regulation of progranulin in neuroblastoma cell lines

Piscopo, Paola; Rivabene, Roberto; Adduci, Alessia; Mallozzi, Cinzia; Malvezzi-Campeggi, Lorenzo; Crestini, Alessio; Confaloni, Annamaria

doi:10.1016/j.neuint.2010.09.008

Cited by 31 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The metabolic stressors acidosis and hypoxia, that are characteristic of tissue trauma, are stimulants for PGRN expression in rat dermal fibroblasts (Guerra et al 2007). PGRN protected dermal fibroblasts against acidotic apoptosis (Guerra et al 2007), and inhibited hypoxic cell death in a neuroblastoma cell line (Piscopo et al 2010). There is growing evidence that PGRN is involved in neuroinflammation.…”

Section: Pgrn In Tissue Injury and Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Structure, Function, and Mechanism of Progranulin; the Brain and Beyond

et al. 2011

View full text Add to dashboard Cite

Mutation of human GRN, the gene encoding the secreted glycoprotein progranulin, results in a form of frontotemporal lobar degeneration that is characterized by the presence of ubiquitinated inclusions containing phosphorylated and cleaved fragments of the transactivation response element DNA-binding protein-43. This has stimulated interest in understanding the role of progranulin in the central nervous system, and in particular, how this relates to neurodegeneration. Progranulin has many roles outside the brain, including regulation of cellular proliferation, survival, and migration, in cancer, including cancers of the brain, in wound repair, and inflammation. It often acts through the extracellular signal-regulated kinase and phopshatidylinositol-3-kinases pathways. The neurobiology of progranulin has followed a similar pattern with proposed roles for progranulin (PGRN) in the central nervous system as a neuroprotective agent and in neuroinflammation. Here we review the structure, biology, and mechanism of progranulin action. By understanding PGRN in a wider context, we may be better able to delineate its roles in the normal brain and in neurodegenerative disease.

show abstract

Section: Pgrn In Tissue Injury and Inflammationmentioning

confidence: 99%

“…Downstream targets of PGRN signaling include nuclear factor kappa-B in myeloma cells (Wang et al 2006) and in chondrocytes, the JunB transcription factor (Feng et al 2010). In addition to stimulating the ERK1/2 activity, PGRN expression is regulated by ERK1/2 signaling (Kamrava et al 2005;Piscopo et al 2010).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Structure, Function, and Mechanism of Progranulin; the Brain and Beyond

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Mechanisms for the regulation of the GRN gene include mRNA stability [124], microRNAs [125][126][127][128], the action of RNA binding proteins [129], signal transduction by MAPK signaling [79], nuclear hormone receptors [130], and by physiological parameters such as hypoxia [87,131].…”

Section: Regulation Of Grn Gene Expressionmentioning

confidence: 99%

“…Both endothelin and LPA promote the expression of the GRN gene [79] through the activation of MAPK by a protein kinase A, calcium and cyclicAMP-dependent mechanism [79]. The up-regulation of GRN gene expression by MAPK may be widespread since it is also reported in neuroblastoma cell lines [131] and in gastric mucosa [51] in response respectively to hypoxia or the presence of the gastritis causing bacterium H. pylori.…”

Section: Regulation Of Grn Gene Expressionmentioning

confidence: 99%

The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Zhang¹

2012

J Carcinogene Mutagene

View full text Add to dashboard Cite

Progranulin (PGRN) is a secreted glycoprotein growth factor with tumorigenic roles in a variety of tumors including, among others, breast, ovarian, prostate, bladder, and liver cancer. In some patients, for example with breast, ovarian or liver cancers, high PGRN expression in tumors correlated with a worse outcome. Studies using cell lines and animal models provide evidence that PGRN promotes tumor cell proliferation, migration and survival, and induces drug resistance. Increasing or decreasing PGRN production enhances or inhibits respectively the growth of PGRN-sensitive tumors in vivo. PGRN activity is associated with p44/42 mitogen-activated protein kinase as well as phosphatidylinositol 3-kinases signaling pathways. In addition, PGRN may stimulate the formation of the tumor stroma. As an extracellular regulator of tumorgenesis, PGRN is a potential therapeutic target and biomarker of prognosis in the treatment of various cancers.

show abstract

“…Mice deficient in PGRN also display impairments in neurite outgrowth [44], [52], neuronal arborization [43], [53], synaptic connectivity and plasticity [43]. These growth factor-like actions, mediated by activation of various cell growth/survival signalling pathways [29], [52], [54]–[56] may promote neuronal repair in response to injury or cellular stress. PGRN may also provide an injured cell with sufficient time for such self-repair by regulating the rate of apoptotic cell clearance [57], [58].…”

Section: Discussionmentioning

confidence: 99%

Progranulin Gene Delivery Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease

Kampen

Baranowski²,

Kay

2014

PLoS ONE

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity and akinesia/bradykinesia resulting from the progressive loss of nigrostriatal dopaminergic neurons. To date, only symptomatic treatment is available for PD patients, with no effective means of slowing or stopping the progression of the disease. Progranulin (PGRN) is a 593 amino acid multifunction protein that is widely distributed throughout the CNS, localized primarily in neurons and microglia. PGRN has been demonstrated to be a potent regulator of neuroinflammation and also acts as an autocrine neurotrophic factor, important for long-term neuronal survival. Thus, enhancing PGRN expression may strengthen the cells resistance to disease. In the present study, we have used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate the possible use of PGRN gene delivery as a therapy for the prevention or treatment of PD. Viral vector delivery of the PGRN gene was an effective means of elevating PGRN expression in nigrostriatal neurons. When PGRN expression was elevated in the SNC, nigrostriatal neurons were protected from MPTP toxicity in mice, along with a preservation of striatal dopamine content and turnover. Further, protection of nigrostriatal neurons by PGRN gene therapy was accompanied by reductions in markers of MPTP-induced inflammation and apoptosis as well as a complete preservation of locomotor function. We conclude that PGRN gene therapy may have beneficial effects in the treatment of PD.

show abstract

Hypoxia induces up-regulation of progranulin in neuroblastoma cell lines

Cited by 31 publications

References 30 publications

Structure, Function, and Mechanism of Progranulin; the Brain and Beyond

Structure, Function, and Mechanism of Progranulin; the Brain and Beyond

The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Progranulin Gene Delivery Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease

Contact Info

Product

Resources

About