Pleiotrophin: Activity and mechanism

Wang, Xu

doi:10.1016/bs.acc.2020.02.003

Cited by 45 publications

(55 citation statements)

References 150 publications

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“…TXNIP is upregulated in diabetes, cardiovascular disease, and neurodegerative disorders [81]. PTN expression can be triggered in tissues by many factors including inflammation and mechanical stress [82]. LSP1 is expressed in hematopoietic lineage and endothelial cells and can contribute to fibrosis in tissues by attracting fibrocytes [83].…”

Section: Discussionmentioning

confidence: 99%

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris

Semba

Zhang

Dufresne

et al. 2021

Proteomics Clinical Apps

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Purpose To characterize the proteome of the iris in primary angle closure glaucoma (PACG). Experimental Design In this cross‐sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography‐tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log2 two‐fold difference in expression in iris between PACG and controls. Results There were 3,446 non‐redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty‐two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN‐2, fibrinogen, fibronectin, matrilin‐2), matricellular proteins (thrombospondin‐1), proteins involved in cell‐matrix interactions (integrins, laminin, histidine‐rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α‐2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up‐ and down‐regulated, respectively, in the iris in PACG compared with controls. Conclusions and Clinical Relevance This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.

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Section: Discussionmentioning

confidence: 99%

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris

Semba

Zhang

Dufresne

et al. 2021

Proteomics Clinical Apps

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“…In addition, there are two types of PTNs: immobilized pleiotrophin (PTN18), which promotes migration via the cell surface receptor, the protein tyrosine phosphatase receptor zeta (PTPRZ1), and soluble pleiotrophin (PTN15), which is mainly involved in promoting glioblastoma proliferation [ 23 ]. PTN is a strong binder of glycosaminoglycans (GAGs) and has been shown to interact with a variety of receptors, including proteoglycans PTPRZ and syndecans and GAG non-containing integrin and nucleolin [ 24 ]. These interactions depend on the sulfation density of GAGs and activate many intracellular kinases, which are involved in cell activation and transformation [ 24 , 25 ].…”

Section: The Characteristics Of Glioma Invasionmentioning

confidence: 99%

“…PTN is a strong binder of glycosaminoglycans (GAGs) and has been shown to interact with a variety of receptors, including proteoglycans PTPRZ and syndecans and GAG non-containing integrin and nucleolin [ 24 ]. These interactions depend on the sulfation density of GAGs and activate many intracellular kinases, which are involved in cell activation and transformation [ 24 , 25 ].…”

Section: The Characteristics Of Glioma Invasionmentioning

confidence: 99%

Molecular Mechanisms and Clinical Challenges of Glioma Invasion

2022

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Glioma is the most common primary brain tumor, and its prognosis is poor. Glioma cells are highly invasive to the brain parenchyma. It is difficult to achieve complete resection due to the nature of the brain tissue, and tumors that invade the parenchyma often recur. The invasiveness of tumor cells has been studied from various aspects, and the related molecular mechanisms are gradually becoming clear. Cell adhesion factors and extracellular matrix factors have a strong influence on glioma invasion. The molecular mechanisms that enhance the invasiveness of glioma stem cells, which have been investigated in recent years, have also been clarified. In addition, it has been discussed from both basic and clinical perspectives that current therapies can alter the invasiveness of tumors, and there is a need to develop therapeutic approaches to glioma invasion in the future. In this review, we will summarize the factors that influence the invasiveness of glioma based on the environment of tumor cells and tissues, and describe the impact of the treatment of glioma on invasion in terms of molecular biology, and the novel therapies for invasion that are currently being developed.

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“…In this context, we here identify Pleiotrophin (PTN) as a novel astrocyte-derived mediator with anti-inflammatory and neuroprotective functions and potential relevance as druggable factor. PTN is a highly conserved developmentally regulated peptide ( 9 ). It is part of the heparin-binding growth factor family of proteins ( 9 ) and is predominantly expressed in nervous tissue ( 10 , 11 ), where it has been described as a growth factor in early embryonic stages ( 12 ) as well as a protooncogene ( 13 ) with highest expression levels in glioblastoma ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…PTN is a highly conserved developmentally regulated peptide ( 9 ). It is part of the heparin-binding growth factor family of proteins ( 9 ) and is predominantly expressed in nervous tissue ( 10 , 11 ), where it has been described as a growth factor in early embryonic stages ( 12 ) as well as a protooncogene ( 13 ) with highest expression levels in glioblastoma ( 9 ). However, growing evidence suggests that PTN also plays a role in degenerative and inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation

et al. 2022

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Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited.

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Pleiotrophin: Activity and mechanism

Cited by 45 publications

References 150 publications

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris

Molecular Mechanisms and Clinical Challenges of Glioma Invasion

Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation

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