Abstract：
:Progranulin (PGRN) is abundantly expressed in epithelial cells, immune cells, neurons, and chondrocytes, and reportedly contributes to tumorigenesis. PGRN is a crucial mediator of wound healing and tissue repair. PGRN also functions as a neurotrophic factor and mutations in the PGRN gene resulting in partial loss of the PGRN protein cause frontotemporal dementia. PGRN has been found to be a novel chondrogenic growth factor and to play an important role in cartilage development and inflammatory arthritis. Although research has shown that PGRN exhibits anti-inflammatory properties, the details about the exact molecular pathway of such effects, and, in particular, the PGRN binding receptor, have not been identified so far. Recently, researchers have shown that PGRN binds to tumor necrosis factor (TNF)-receptors (TNFR), interfering with the interaction between TNFα and TNFR. They further demonstrated that mice deficient in PGRN are susceptible to collagen-induced arthritis, an experimental model of rheumatoid arthritis, and that administration of PGRN reversed the arthritic process. An engineered protein made of three PGRN fragments (Atsttrin), displayed selective TNFR binding and was more active than natural PGRN. Both PGRN and Atsttrin prevented inflammation in various arthritis mouse models and inhibited TNFα-induced intracellular signaling pathways. Thus, PGRN is a key regulator of inflammation and it may mediate its anti-inflammatory effects, at least in part, by blocking TNF binding to its receptors. As we discuss here, TNFR-based interventions may both stimulate and suppress the growth of cancer cells, and the same may be true in analogy for Atsttrin as a new player.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Liu CJ,Bosch Xdoi
10.1016/j.pharmthera.2011.10.003subject
Has Abstractpub_date
2012-01-01 00:00:00pages
124-32issue
1eissn
0163-7258issn
1879-016Xpii
S0163-7258(11)00188-4journal_volume
133pub_type
杂志文章,评审abstract：:Multiple sclerosis (MS) is the commonest cause of progressive neurological disability amongst young, Caucasian adults. MS is considered to be an auto-immune disease that results from an attack against myelin, the layer which surrounds axons. The pathophysiology of MS is complex, with both demyelination and axonal dege...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90039-o
更新日期：1991-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00012-6
更新日期：1995-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00001-w
更新日期：1995-04-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90029-l
更新日期：1991-12-01 00:00:00
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journal_title：Pharmacology & therapeutics
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更新日期：2020-09-01 00:00:00
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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更新日期：2007-11-01 00:00:00
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
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更新日期：2000-07-01 00:00:00
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journal_title：Pharmacology & therapeutics
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更新日期：2018-03-01 00:00:00
abstract：:Pericytes and other perivascular stem cells are of growing interest in orthopedics and tissue engineering. Long regarded as simple regulators of angiogenesis and blood pressure, pericytes are now recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory...
journal_title：Pharmacology & therapeutics
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更新日期：2017-03-01 00:00:00
abstract：:Proteolytic degradation of unwanted proteins by the ubiquitin-proteasome system (UPS) is critical for normal maintenance of various cellular functions. Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders, is characterized by prominent and irreversible nigral dopaminergic neuronal loss and i...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2007-06-01 00:00:00
abstract：:Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL (OxLDL) in endothelial cells. Its inducible expression in macrophages and smooth muscle cell was also observed. LOX-1 is a Type II membrane protein with a typical C-type lectin structur...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2002-07-01 00:00:00
abstract：:Recent epidemiologic studies have shown that aerobic exercise, one of lifestyle modifications, reduces cardiovascular morbidity and mortality in the general population. However, the mechanisms underlying the anti-atherogenic and anti-hypertensive effects of exercise remain unclear. Hypertension is associated with alte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.02.003
更新日期：2004-04-01 00:00:00
abstract：:There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids. However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous syste...
journal_title：Pharmacology & therapeutics
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doi：10.1016/j.pharmthera.2012.12.004
更新日期：2013-03-01 00:00:00
