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Heather A Himburg, Christina M Termini, Lauren Schlussel, Jenny Kan, Michelle Li, Liman Zhao, Tiancheng Fang, Joshua P Sasine, Vivian Y Chang, John P Chute
Bone marrow (BM) perivascular stromal cells and vascular endothelial cells (ECs) are essential for hematopoietic stem cell (HSC) maintenance, but the roles of distinct niche compartments during HSC regeneration are less understood. Here we show that Leptin receptor-expressing (LepR+) BM stromal cells and ECs dichotomously regulate HSC maintenance and regeneration via secretion of pleiotrophin (PTN). BM stromal cells are the key source of PTN during steady-state hematopoiesis because its deletion from stromal cells, but not hematopoietic cells, osteoblasts, or ECs, depletes the HSC pool...
July 30, 2018: Cell Stem Cell
Zhan Gao, Baozhen Qu, Lan Yao, Zengyu Ma, Pengfei Cui, Shicui Zhang
Midkine (MK) and pleiotrophin (PTN) are the only two members of heparin-binding growth factor family. MK/PTN homologues found from Drosophila to humans are shown to have antibacterial activities and their antibacterial domains are conserved during evolution. However, little is known about MK/PTN homologue in the basal chordate amphioxus, and overall, information regarding MK/PTN homologues is rather limited in invertebrates. In this study, we identified a single MK/PTN homologue in Branchiostoma japonicum, termed BjMiple, which has a novel domain structure of PTN-PTNr1-PTNr2, and represents the ancestral form of vertebrate MK/PTN family proteins...
August 7, 2018: Developmental and Comparative Immunology
Nesreen Zoghoul Alsmadi, Geetanjali S Bendale, Aswini Kanneganti, Tarik Shihabeddin, An H Nguyen, Elijah Hor, Swarup Dash, Benjamin Johnston, Rafael Granja-Vazquez, Mario I Romero-Ortega
The repair of nerve gap injuries longer than 3 cm is limited by the need of sacrifice donor tissue and morbidity associated with the autograft gold standard, while decellularized grafts and biodegradable conduits are effective only in short nerve defects. The advantage of isogenic nerve implants seems to be the release of various growth factors by the denervated Schwann cells. We evaluated the effect of vascular endothelial growth factor, neurotrophins, and pleiotrophin (PTN) supplementation of multi-luminal conduits, in the repair of 3 and 4 cm nerve gaps in the rabbit peroneal nerve...
July 27, 2018: Acta Biomaterialia
Pei-Song Bai, Peng Hou, Ying Kong
Hepatocellular carcinoma (HCC) is a male-dominant cancer. Several factors may contribute to the gender difference. Recent investigations have reported that miRNAs are involved in sex-linked signaling pathways and play a critical role in the molecular pathogenesis of hepatitis B virus (HBV)-related HCC. Therefore, we speculated that some of these miRNAs might contribute to the gender differences observed in HBV-related HCC. Our results showed that miR-371a-5p was significantly upregulated in tumor tissue and serum from HCC patients and that the expression level of miR-371a-5p was related to HBV infection, sexuality, TNM stage, adjacent organ invasion and microvascular invasion...
June 19, 2018: Experimental Cell Research
Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Miryam Pastor, Esther Gramage, Bruno Di Geronimo, José María Zapico, Claire Coderch, Carmen Pérez-García, Amy W Lasek, Beatriz de Pascual-Teresa, Ana Ramos, Gonzalo Herradón
Pleiotrophin (PTN) and Midkine (MK) are neurotrophic factors that are upregulated in the prefrontal cortex after alcohol administration and have been shown to reduce ethanol drinking and reward. PTN and MK are the endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1, RPTPβ, PTPζ), suggesting a potential role for this phosphatase in the regulation of alcohol effects. To determine if RPTPβ/ζ regulates ethanol consumption, we treated mice with recently developed small-molecule inhibitors of RPTPβ/ζ (MY10, MY33-3) before testing them for binge-like drinking using the drinking in the dark protocol...
July 15, 2018: Neuropharmacology
Evgenia Lampropoulou, Ioanna Logoviti, Marina Koutsioumpa, Maria Hatziapostolou, Christos Polytarchou, Spyros S Skandalis, Ulf Hellman, Manolis Fousteris, Sotirios Nikolaropoulos, Efrosini Choleva, Margarita Lamprou, Angeliki Skoura, Vasileios Megalooikonomou, Evangelia Papadimitriou
Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and αν β3 integrin. Screening for proteins that interact with RPTPβ/ζ and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclin-dependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration...
April 12, 2018: Scientific Reports
Chi Hua Sarah Lin, Yu Zhang, Kenneth Kaushansky, Huichun Zhan
Myeloproliferative neoplasms are clonal stem cell disorders characterized by hematopoietic stem/progenitor cell expansion. The acquired kinase mutation JAK2V617F plays a central role in these disorders. Abnormalities of the marrow microenvironment are beginning to be recognized as an important factor in the development of myeloproliferative neoplasms. Endothelial cells are an essential component of the hematopoietic vascular niche. Endothelial cells carrying the JAK2V617F mutation can be detected in patients with myeloproliferative neoplasms, suggesting that the mutant vascular niche is involved in the pathogenesis of these disorders...
July 2018: Haematologica
Li-Qiang Liu, Li-Fei Feng, Cheng-Rui Nan, Zong-Mao Zhao
The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR...
May 29, 2018: Bioscience Reports
Honggang Sun, Liqin He, Lan Ma, Tao Lu, Jianguo Wei, Kejie Xie, Xingmu Wang
Thyroid cancer is one of the most prevalent endocrine neoplasm. The present study examined the effects of Colorectal Neoplasia Differentially Expressed (CRNDE) on the progression of papillary thyroid cancer (PTC), and explored the underlying molecular mechanisms. Quantitative real-time PCR was used to detect CRNDE, miR-384 and pleiotrophin (PTN) mRNA expression. Western blot was used to measure PTN protein levels. Cell proliferation, cell growth, cell invasion and migration of PTC cells were determined by CCK-8, colony formation, transwell invasion and migration assays, respectively...
December 15, 2017: Oncotarget
Rui Wang, Yuxing Cai, Baoping Zhang, Zhengxia Wu
The present study aimed to perform screening of a gene signature for the discrimination and prognostic prediction of stage I and II lung squamous carcinoma. A microarray meta‑analysis was performed to identify differentially expressed genes (DEGs) between stage I and II lung squamous carcinoma samples in seven microarray datasets collected from the Gene Expression Omnibus database via the MetaQC and MetaDE package in R. The important DEGs were selected according to the betweenness centrality value of the protein‑protein interaction (PPI) network...
March 2018: International Journal of Molecular Medicine
Miryam Pastor, Rosalía Fernández-Calle, Bruno Di Geronimo, Marta Vicente-Rodríguez, José María Zapico, Esther Gramage, Claire Coderch, Carmen Pérez-García, Amy W Lasek, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Beatriz de Pascual-Teresa, Gonzalo Herradón, Ana Ramos
A new series of blood-brain barrier permeable molecules designed to mimic the activity of Pleiotrophin in the CNS has been designed and synthesized. These compounds exert their action by interacting with the intracellular domain PD1 of the Protein Tyrosine-Phosphatase Receptor Z1 (PTPRZ1), and inhibiting its tyrosine phosphatase activity. The most potent compounds 10a and 12b (IC50  = 0,1 μM) significantly increase the phosphorylation of key tyrosine residues of PTPRZ1 substrates involved in neuronal survival and differentiation, and display protective effects against amphetamine-induced toxicity...
January 20, 2018: European Journal of Medicinal Chemistry
Binqing Fu, Yonggang Zhou, Xiang Ni, Xianhong Tong, Xiuxiu Xu, Zhongjun Dong, Rui Sun, Zhigang Tian, Haiming Wei
Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy. However, the role of NK cells in fetal growth is unclear. Here, we have identified a CD49a+ Eomes+ subset of NK cells that secreted growth-promoting factors (GPFs), including pleiotrophin and osteoglycin, in both humans and mice. The crosstalk between HLA-G and ILT2 served as a stimulus for GPF-secreting function of this NK cell subset. Decreases in this GPF-secreting NK cell subset impaired fetal development, resulting in fetal growth restriction...
December 19, 2017: Immunity
Gimena Gomez, Mariano D Saborido, M Alejandra Bernardi, Oscar S Gershanik, Irene R Taravini, Juan E Ferrario
L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats...
February 14, 2018: Neuroscience Letters
Yuki Takakura, Noritaka Yamaguchi, Takuya Honda, Mariko Morii, Ryuzaburo Yuki, Yuji Nakayama, Naoto Yamaguchi
Anaplastic lymphoma kinase (ALK) is a receptor-type tyrosine kinase that promotes cell growth upon stimulation with ligands such as midkine and pleiotrophin. Recently, a truncated isoform of ALK was identified in a variety of tumors. This isoform is expressed from a novel ALK transcript initiated from a de novo alternative transcription initiation (ATI) site in ALK intron 19 (referred to as ALKATI ). ALKATI , which consists of only the intracellular kinase domain, localizes to the nucleus as well as the cytoplasm...
2017: Biological & Pharmaceutical Bulletin
Sanjay Anand, Vidhi Desai, Nesreen Alsmadi, Aswini Kanneganti, Dianna Huyen-Tram Nguyen, Martin Tran, Lokesh Patil, Srikanth Vasudevan, Cancan Xu, Yi Hong, Jonathan Cheng, Edward Keefer, Mario I Romero-Ortega
Neural interfaces are designed to decode motor intent and evoke sensory precepts in amputees. In peripheral nerves, recording movement intent is challenging because motor axons are only a small fraction compared to sensory fibers and are heterogeneously mixed particularly at proximal levels. We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve guide with sealed ends, can be modulated by luminar release of nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively...
October 30, 2017: Scientific Reports
Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Esther Gramage, Carlos de la Torre-Ortiz, Carmen Pérez-García, María P Ramos, Gonzalo Herradón
Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate neuroinflammation. PTN overexpression in the brain prevents LPS-induced astrocytosis in mice but potentiates microglial activation. The modest astrocytic response caused by a low dose of LPS (0.5mg/kg) is blocked in the striatum of MK-/- mice whereas microglial response is unaffected. We have now tested the effects of an intermediate dose of LPS (7.5mg/kg) in glial response in PTN-/- and MK-/- mice. We found that LPS-induced astrocytosis is prevented in prefrontal cortex and striatum of both PTN-/- and MK-/- mice...
January 1, 2018: Neuroscience Letters
Tobias Skillbäck, Niklas Mattsson, Karl Hansson, Ekaterina Mirgorodskaya, Rahil Dahlén, Wiesje van der Flier, Philip Scheltens, Floor Duits, Oskar Hansson, Charlotte Teunissen, Kaj Blennow, Henrik Zetterberg, Johan Gobom
We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra...
October 17, 2017: Scientific Reports
Dapeng Wu, Liguo Liu, Xuebing Yan, Chunyan Wang, Yaling Wang, Kun Han, Shuchen Lin, Zhihua Gan, Daliu Min
Chemoresistance is a major hindrance to successful treatment of osteosarcoma (OS). Pleiotrophin (PTN), a neurotrophic growth factor, has been linked to the malignant characteristics of various cancer types. We retrospectively examined the correlation between PTN expression and chemoresistance in OS in a cohort of 133 OS patients. Immunohistochemistry revealed that PTN expression correlated with the necrosis rate and local OS recurrence. In a prognostic analysis, high PTN expression was associated with poor overall and disease-free survival, and was an independent adverse prognostic factor for disease-free survival...
September 8, 2017: Oncotarget
Nicole M Giamanco, Youn Hee Jee, Anton Wellstein, Craig D Shriver, Thomas A Summers, Jeffrey Baron
BACKGROUND/OBJECTIVE: Midkine (MDK) and pleiotrophin (PTN) are two closely related heparin-binding growth factors which are overexpressed in a wide variety of human cancers. We hypothesized that the concentrations of these factors in washout of biopsy needles would be higher in breast and lung cancer than in benign lesions. METHODS: Seventy subjects underwent pre-operative core needle biopsies of 78 breast masses (16 malignancies). In 11 subjects, fine needle aspiration was performed ex vivo on 7 non-small cell lung cancers and 11 normal lung specimens within surgically excised lung tissue...
September 7, 2017: Cancer Biomarkers: Section A of Disease Markers
Di Shen, Nataly P Podolnikova, Valentin P Yakubenko, Christopher L Ardell, Arnat Balabiyev, Tatiana P Ugarova, Xu Wang
Pleiotrophin (PTN) is a multifunctional, cationic, glycosaminoglycan-binding cytokine and growth factor involved in numerous physiological and pathological processes, including tissue repair and inflammation-related diseases. PTN has been shown to promote leukocyte responses by inducing their migration and expression of inflammatory cytokines. However, the mechanisms through which PTN mediates these responses remain unclear. Here, we identified the integrin Mac-1 (αMβ2, CD11b/CD18) as the receptor mediating macrophage adhesion and migration to PTN...
November 17, 2017: Journal of Biological Chemistry
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