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https://www.readbyqxmd.com/read/28052876/pericyte-and-immune-cells-contribute-to-complement-activation-in-tubulointerstitial-fibrosis
#1
Sandhya Xavier, Ranjit K Sahu, Susan G Landes, Jing Yu, Ronald P Taylor, Srinivas Ayyadevara, Judit Megyesi, William B Stallcup, Jeremy S Duffield, Edimara S Reis, John D Lambris, Didier Portilla
We have examined the pathogenic role of increased complement expression and activation during kidney fibrosis. Here we show that PDGFRβ positive pericytes isolated from mice subjected to obstructive or folic acid injury secrete C1q. This was associated with increased production of proinflammatory cytokines, extracellular matrix components, collagens and increased Wnt3a-mediated activation of Wnt/β-catenin signaling, that are hallmarks of myofibroblast activation. Real-time PCR, immunoblots, immunohistochemistry and flow cytometry analysis performed in whole kidney tissue confirmed increased expression of C1q, C1r, C1s as well as complement activation measured as increased synthesis of C3 fragments predominantly in the interstitial compartment...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28030611/silibinin-inhibits-platelet-derived-growth-factor-driven-cell-proliferation-via-downregulation-of-n-glycosylation-in-human-tenon-s-fibroblasts-in-a-proteasome-dependent-manner
#2
Yi-Hao Chen, Ching-Long Chen, Da-Wen Lu, Chang-Min Liang, Ming-Cheng Tai, Jiann-Torng Chen
The objective of this study was to evaluate the effects of silibinin on cell proliferation in platelet-derived growth factor (PDGF)-treated human Tenon's fibroblasts (HTFs). The effect of silibinin on cell proliferation in PDGF-treated HTFs was determined by examining the expression of proliferating cell nuclear antigen (PCNA) and performing WST-1 assays. Cell cycle progression was evaluated using flow cytometry. The related cyclins and cyclin-dependent kinases (CDKs) were also analyzed using western blot. A modified rat trabeculectomy model was established to evaluate the effect of silibinin on cell proliferation in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/28018977/heterogeneous-perivascular-cell-coverage-affects-breast-cancer-metastasis-and-response-to-chemotherapy
#3
Jiha Kim, Pedro Correa de Sampaio, Donna Marie Lundy, Qian Peng, Kurt W Evans, Hikaru Sugimoto, Mihai Gagea, Yvonne Kienast, Nayra Soares do Amaral, Rafael Malagoli Rocha, Hans Petter Eikesdal, Per Eystein Lønning, Funda Meric-Bernstam, Valerie S LeBleu
Angiogenesis and co-optive vascular remodeling are prerequisites of solid tumor growth. Vascular heterogeneity, notably perivascular composition, may play a critical role in determining the rate of cancer progression. The contribution of vascular pericyte heterogeneity to cancer progression and therapy response is unknown. Here, we show that angiopoietin-2 (Ang2) orchestrates pericyte heterogeneity in breast cancer with an effect on metastatic disease and response to chemotherapy. Using multispectral imaging of human breast tumor specimens, we report that perivascular composition, as defined by the ratio of PDGFRβ(-) and desmin(+) pericytes, provides information about the response to epirubicin but not paclitaxel...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/27980069/multiple-routes-of-endocytic-internalization-of-pdgfr%C3%AE-contribute-to-pdgf-induced-stat3-signaling
#4
Kamil Jastrzębski, Daria Zdżalik-Bielecka, Agnieszka Mamińska, Yannis Kalaidzidis, Carina Hellberg, Marta Miaczynska
Platelet-derived growth factor receptor β (PDGFRβ) is a receptor tyrosine kinase which upon activation by PDGF-BB stimulates cell proliferation, migration and angiogenesis. Ligand binding induces intracellular signaling cascades but also internalization of the receptor, eventually resulting in its lysosomal degradation. However, endocytic trafficking of receptors often modulates their downstream signaling. We previously reported that internalization of PDGFRβ occurs via dynamin-dependent and -independent pathways but their further molecular determinants remained unknown...
December 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27922607/endocytosis-following-dopamine-d2-receptor-activation-is-critical-for-neuronal-activity-and-dendritic-spine-formation-via-rabex-5-pdgfr%C3%AE-signaling-in-striatopallidal-medium-spiny-neurons
#5
N Shioda, Y Yabuki, Y Wang, M Uchigashima, T Hikida, T Sasaoka, H Mori, M Watanabe, M Sasahara, K Fukunaga
Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-β (PDGFRβ)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27908803/pericytes-integral-components-of-adult-hematopoietic-stem-cell-niches
#6
REVIEW
D Sá da Bandeira, J Casamitjana, M Crisan
The interest in perivascular cells as a niche for adult hematopoietic stem cells (HSCs) is significantly growing. In the adult bone marrow (BM), perivascular cells and HSCs cohabit. Among perivascular cells, pericytes are precursors of mesenchymal stem/stromal cells (MSCs) that are capable of differentiating into osteoblasts, adipocytes and chondrocytes. In situ, pericytes are recognised by their localisation to the abluminal side of the blood vessel wall and closely associated with endothelial cells, in combination with the expression of markers such as CD146, neural glial 2 (NG2), platelet derived growth factor receptor β (PDGFRβ), α-smooth muscle actin (α-SMA), nestin (Nes) and/or leptin receptor (LepR)...
November 28, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27885822/from-type%C3%A2-i-to-type%C3%A2-ii-design-synthesis-and-characterization-of-potent-pyrazin-2-ones-as-dfg-out-inhibitors-of-pdgfr%C3%AE
#7
Eugen Bethke, Boris Pinchuk, Christian Renn, Lydia Witt, Joachim Schlosser, Christian Peifer
Reversible protein kinase inhibitors that bind in the ATP cleft can be classified as type I or type II binders. Of these, type I inhibitors address the active form, whereas type II inhibitors typically lock the kinase in an inactive form. At the molecular level, the conformation of the flexible activation loop holding the key DFG motif controls access to the ATP site, thereby determining an active or inactive kinase state. Accordingly, type I and type II kinase inhibitors bind to so-called DFG-in or DFG-out conformations, respectively...
December 16, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27881889/expression-of-caf-related-proteins-is-associated-with-histologic-grade-of-breast-phyllodes-tumor
#8
Hye Min Kim, Yu Kyung Lee, Ja Seung Koo
Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p = 0...
2016: Disease Markers
https://www.readbyqxmd.com/read/27856617/pdgfr%C3%AE-regulates-craniofacial-development-through-homodimers-and-functional-heterodimers-with-pdgfr%C3%AE
#9
Katherine A Fantauzzo, Philippe Soriano
Craniofacial development is a complex morphogenetic process, disruptions in which result in highly prevalent human birth defects. While platelet-derived growth factor (PDGF) receptor α (PDGFRα) has well-documented functions in this process, the role of PDGFRβ in murine craniofacial development is not well established. We demonstrate that PDGFRα and PDGFRβ are coexpressed in the craniofacial mesenchyme of mid-gestation mouse embryos and that ablation of Pdgfrb in the neural crest lineage results in increased nasal septum width, delayed palatal shelf development, and subepidermal blebbing...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27821319/a-phase-ii-study-of-sorafenib-in-recurrent-and-or-metastatic-salivary-gland-carcinomas-translational-analyses-and-clinical-impact
#10
L D Locati, F Perrone, B Cortelazzi, C Bergamini, P Bossi, E Civelli, C Morosi, S Lo Vullo, M Imbimbo, P Quattrone, G P Dagrada, R Granata, C Resteghini, A Mirabile, S Alfieri, E Orlandi, L Mariani, G Saibene, S Pilotti, L Licitra
BACKGROUND: Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β, RET, KIT)...
November 4, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27803296/homocysteine-deteriorates-intrahepatic-derangement-and-portal-systemic-collaterals-in-cirrhotic-rats
#11
Hung-Chun Tung, Shao-Jung Hsu, Ming-Hung Tsai, Te-Yueh Lin, I-Fang Hsin, Te-Ia Huo, Fa-Yauh Lee, Hui-Chun Huang, Hsin-Ling Ho, Han-Chieh Lin, Shou-Dong Lee
In liver cirrhosis, the altered levels of vasoactive substances, especially endothelin-1 (ET-1) and nitric oxide (NO) lead to elevated intrahepatic resistance, increased portal-systemic collaterals and abnormal intra- and extra-hepatic vascular responsiveness. These derangements aggravate portal hypertension-related complications such as gastro-oesophageal variceal bleeding. Homocysteine, a substance implicated in cardiovascular diseases, has been found with influences on vasoresponsiveness and angiogenesis...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27793148/pdgfr%C3%AE-c-kit-pulp-cells-are-odontoblastic-progenitors-capable-of-producing-dentin-like-structure-in-vitro-and-in-vivo
#12
Shiwei Cai, Wenjian Zhang, Wei Chen
BACKGROUND: Successful pulp regeneration depends on identification of pulp stem cells capable of differentiation under odontoblastic lineage and producing pulp-dentinal like structure. Recent studies demonstrate that platelet-derived growth factor (PDGF) plays an important role in damage repair and tissue regeneration. The aim of this study was to identify a subpopulation of dental pulp cells responsive to PDGF and with dentin regeneration potential. METHODS: Pulp tissues were isolated from 12 freshly extracted human impacted third molars...
October 28, 2016: BMC Oral Health
https://www.readbyqxmd.com/read/27779900/ablation-of-pericyte-like-cells-in-lungs-by-oropharyngeal-aspiration-of-diphtheria-toxin
#13
Chi F Hung, Yu-Hua Chow, W Conrad Liles, William A Altemeier, Lynn M Schnapp
: We previously demonstrated that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspiration as an approach to ablate FoxD1-derived cells. METHOD: We crossed mice expressing Cre-recombinase under the FoxD1 promoter to Rosa26-loxP-STOP-loxP-iDTR mice and generated a bitransgenic line (FoxD1-Cre;Rs26-iDTR) where FoxD1-derived cells heritably express iDTR and are sensitive to DT...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27778377/dynamics-of-pdgfr%C3%AE-expression-in-different-cell-types-after-brain-injury
#14
Jenni Kyyriäinen, Xavier Ekolle Ndode-Ekane, Asla Pitkänen
Platelet-derived growth factor receptor β (PDGFRβ) is upregulated after brain injury and its depletion results in the blood-brain barrier (BBB) damage. We investigated the time-window and localization of PDGFRβ expression in mice with intrahippocampal kainic acid-induced status epilepticus (SE) and in rats with lateral fluid-percussion-induced traumatic brain injury (TBI). Tissue immunohistochemistry was evaluated at several time-points after SE and TBI. The distribution of PDGFRβ was analyzed, and its cell type-specific expression was verified with double/triple-labeling of astrocytes (GFAP), NG2 cells, and endothelial cells (RECA-1)...
February 2017: Glia
https://www.readbyqxmd.com/read/27764516/characteristics-of-the-expression-of-kai1-cd82-and-pdgfr%C3%AE-and-their-impact-on-glioma-progression
#15
M Paradowski, M Bilinska, J Bar
The biological features of glioma cells may define their clinical outcome. Little is known about the interactions between KAI1/CD82 metastatic suppressor protein and PDGFR in gliomas. The aim of the study was to examine KAI1/CD82 and PDGFR expression in gliomas in order to find the impact of these proteins on progression of the tumors. PDGFR, KAI1/CD82 protein expression and mRNA of genes were evaluated on eighty four paraffin-embedded tissue of gliomas using immunohistochemical staining and RT-PCR analysis...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27751871/hif1%C3%AE-induced-pdgfr%C3%AE-signaling-promotes-developmental-hsc-production-via-il-6-activation
#16
Sung-Eun Lim, Virginie Esain, Wanda Kwan, Lindsay N Theodore, Mauricio Cortes, Isaura M Frost, Sarah Y Liu, Trista E North
Hematopoietic stem cells (HSCs) have the ability to both self-renew and differentiate each of the mature blood cell lineages and thereby reconstitute the entire blood system. Therefore, HSCs are therapeutically valuable for treatment of hematological malignances and bone marrow failure. We showed recently that transient glucose elevation elicited dose-dependent effects on HSCs through elevated metabolic activity and subsequent reactive oxygen species-mediated induction of Hypoxia-Inducible Factor 1α (Hif1α)...
October 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27742657/chromoplectic-tpm3-alk-rearrangement-in-a-patient-with-inflammatory-myofibroblastic-tumor-who-responded-to-ceritinib-after-progression-on-crizotinib
#17
A S Mansfield, S J Murphy, F R Harris, S I Robinson, R S Marks, S H Johnson, J B Smadbeck, G C Halling, E S Yi, D Wigle, G Vasmatzis, J Jen
BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy...
November 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27737004/tyrosine-kinase-inhibitors-regulate-opg-through-inhibition-of-pdgfr%C3%AE
#18
Susannah O'Sullivan, Mei Lin Tay, Jian-Ming Lin, Usha Bava, Karen Callon, Jillian Cornish, Dorit Naot, Andrew Grey
Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG). In the current work we report that platelet-derived growth factor receptor beta (PDGFRβ) signaling regulates OPG production in vitro...
2016: PloS One
https://www.readbyqxmd.com/read/27736501/validation-of-cross-species-reactivity-of-the-vegf-a-pdgfr%C3%AE-bifunctional-antibody-pf-06653157
#19
Roshan Ashoor, Dong Lee, Alvan Cheng, Bart Jessen, Wenhu Huang
PURPOSE: PF-06653157 is a bifunctional antagonist monoclonal antibody (mAb) that targets human VEGF-A ligand and PDGF-Rβ. With the advent of PF-06653157 as an angiogenesis inhibitor and potential treatment for angiogenesis deregulation diseases, a relevant toxicology species is needed for toxicity and efficacy studies. Investigative studies were conducted to validate the mAb dual antagonist properties in a human system and determine its cross-reactive pharmacology in nonhuman cells. METHODS: Sequence alignment was used to determine percent sequence identity of VEGF and PDGF receptors and ligands; qualitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the presence of PDGF-Rβ on cells of interest...
December 2016: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27698080/tyrosine-kinase-receptor-expression-in-canine-liposarcoma
#20
G Avallone, V Pellegrino, P Roccabianca, E Lepri, L Crippa, G Beha, L De Tolla, G Sarli
The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP...
October 3, 2016: Veterinary Pathology
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