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https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#1
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28436498/integrative-meta-modeling-identifies-endocytic-vesicles-late-endosome-and-the-nucleus-as-the-cellular-compartments-primarily-directing-rtk-signaling
#2
Jared C Weddell, Princess I Imoukhuede
Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling...
April 24, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28433542/blockade-of-pdgf-receptors-by-crenolanib-has-therapeutic-effect-in-patient-fibroblasts-and-in-preclinical-models-of-systemic-sclerosis
#3
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Julio C Mantero, Robert Lafyatis, Robert Simms, Maria Trojanowska
Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. PDGF, a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II (Ang II)-induced skin and heart fibrosis...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28424212/pdgf-receptor-%C3%AE-uses-akt-mtorc1-signaling-node-to-promote-high-glucose-induced-renal-proximal-tubular-cell-collagen-i-%C3%AE-2-expression
#4
Falguni Das, Nandini Ghosh-Choudhury, Balachandar Venkatesan, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
Increased expression of PDGF receptor-β (PDGFRβ) has been shown in the diabetic renal proximal tubules. The core molecular network used by high glucose to induce proximal tubular epithelial cell collagen I (α2) expression is poorly understood. We hypothesized that activation of PDGFRβ by high glucose increases collagen I (α2) production via Akt/mTORC1 signaling pathway in proximal tubular epithelial cells. Using biochemical and molecular biological techniques, we investigated this hypothesis. We show that high glucose increases activating phosphorylation of the PDGFRβ, resulting in the phosphorylation of the phosphatidylinositol 3 kinase...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28362700/dermatofibrosarcoma-protuberans-an-immunomarker-study-of-57-cases-that-included-putative-mesenchymal-stem-cell-markers
#5
Joon Seon Song, Eun-Ju Kim, Chan-Sik Park, Kyung-Ja Cho
Dermatofibrosarcoma protuberans (DFSP) is a low-grade fibroblastic sarcoma with a superficial location that has been suggested to potentially be a type of mesenchymal stem cell tumor. We studied the expression of various immunomarkers, including putative stem cell markers, in a series of 57 DFSPs including variants, and 12 dermatofibromas (DFs). CD105, a mesenchymal stem cell marker, was weakly expressed in 24 DFSPs, whereas other stem cell markers, including CD133, ALK-1, and Oct3/4, were completely negative in all samples...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28345526/aspects-of-pericytes-and-their-potential-therapeutic-use
#6
Justyna Różycka, Edyta Brzóska, Tomasz Skirecki
Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2), β-type platelet-derived growth factor receptor (PDGFRβ), smooth muscle α-actin (α-SMA), regulator of G protein signalling 5 (RGS5), the adhesion protein CD146 and nestin...
March 13, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28339027/su6668-modulates-prostate-cancer-progression-by-downregulating-mtdh-akt-signaling-pathway
#7
Benjiang Qian, Yi Yao, Changming Liu, Jiabing Zhang, Huihong Chen, Huizhang Li
Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRβ and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28333941/phenotypically-heterogeneous-podoplanin-expressing-cell-populations-are-associated-with-the-lymphatic-vessel-growth-and-fibrogenic-responses-in-the-acutely-and-chronically-infarcted-myocardium
#8
Maria Cimini, Antonio Cannatá, Gianandrea Pasquinelli, Marcello Rota, Polina Goichberg
Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts...
2017: PloS One
https://www.readbyqxmd.com/read/28289267/dual-role-of-pericyte-%C3%AE-6%C3%AE-1-integrin-in-tumour-blood-vessels
#9
Louise E Reynolds, Gabriela D'Amico, Tanguy Lechertier, Alexandros Papachristodoulou, José M Muñoz-Félix, Adèle De Arcangelis, Marianne Baker, Bryan Serrels, Kairbaan M Hodivala-Dilke
The integrin α6β1 is a major laminin receptor, and formation of a laminin-rich basement membrane is a key feature in tumour blood vessel stabilisation and pericyte recruitment; processes that are important in the growth and maturation of tumour blood vessels. However, the role of pericyte α6β1-integrin in angiogenesis is largely unknown. We developed mice where the α6-integrin subunit is deleted in pericytes and examined tumour angiogenesis and growth. These mice had: i) reduced pericyte coverage of tumour blood vessels; ii) reduced tumour blood vessel stability; iii) increased blood vessel diameter; iv) enhanced leakiness and, v) abnormal blood vessel basement membrane architecture...
March 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28268217/a-phenanthrene-derivative-5-7-dimethoxy-1-4-phenanthrenequinone-inhibits-cell-adhesion-molecule-expression-and-migration-in-vascular-endothelial-and-smooth-muscle-cells
#10
Huey-Ming Lo, Tsong-Long Hwang, Wen-Bin Wu
The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs...
2017: Pharmacology
https://www.readbyqxmd.com/read/28259995/microrna-182-prevents-vascular-smooth-muscle-cell-dedifferentiation-via-fgf9-pdgfr%C3%AE-signaling
#11
Nana Dong, Wei Wang, Jinwei Tian, Zulong Xie, Bo Lv, Jiannan Dai, Rui Jiang, Dan Huang, Shaohong Fang, Jiangtian Tian, Hulun Li, Bo Yu
The abnormal phenotypic transformation of vascular smooth muscle cells (SMCs) causes various proliferative vascular diseases. MicroRNAs (miRNAs or miRs) have been established to play important roles in SMC biology and phenotypic modulation. This study revealed that the expression of miR‑182 was markedly altered during rat vascular SMC phenotypic transformation in vitro. We aimed to investigate the role of miR‑182 in the vascular SMC phenotypic switch and to determine the potential molecular mechanisms involved...
April 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28254885/neuropilin-1-binds-pdgf-d-and-is-a-co-receptor-in-pdgf-d-pdgfr%C3%AE-signaling
#12
Lars Muhl, Erika Bergsten Folestad, Hanna Gladh, Yixin Wang, Christine Moessinger, Lars Jakobsson, Ulf Eriksson
Platelet-derived growth factor (PDGF)-D is a PDGF receptor β (PDGFRβ)-specific ligand implicated in a number of pathological conditions, such as cardiovascular disease and cancer, but its biological function remains incompletely understood. In this study, we demonstrate that PDGF-D binds directly to neuropilin 1 (NRP1), in a manner that requires the PDGF-D C-terminal Arg residue. Stimulation with PDGF-D, but not PDGF-B, induced PDGFRβ-NRP1 complex formation in fibroblasts. Additionally, PDGF-D induced translocation of NRP1 to cell-cell junctions in endothelial cells, independently of PDGFRβ, altering the availability of NRP1 for VEGF-A-VEGFR2 signaling...
April 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28220032/pharmacologic-blockade-of-%C3%AE-v%C3%AE-1-integrin-ameliorates-renal-failure-and-fibrosis-in-vivo
#13
Yongen Chang, Wei Ling Lau, Hyunil Jo, Kazuyuki Tsujino, Leslie Gewin, Nilgun Isik Reed, Amha Atakilit, Ane Claudia Fernandes Nunes, William F DeGrado, Dean Sheppard
Activated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells in vivo is poorly understood. PDGF receptor β (PDGFRβ) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFRβ promoter-driven Cre system to delete αv integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFRβ-Cre line to isolate and study renal fibroblasts ex vivo We found that renal fibroblasts express three αv integrins, namely αvβ1, αvβ3, and αvβ5...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28196027/mk2461-a-multitargeted-kinase-inhibitor-suppresses-the-progression-of-pancreatic-cancer-by-disrupting-the-interaction-between-pancreatic-cancer-cells-and-stellate-cells
#14
Koetsu Inoue, Hideo Ohtsuka, Masanori Tachikawa, Fuyuhiko Motoi, Masahiro Shijo, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno, Tetsuya Terasaki
OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRβ) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRβ, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRβ and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#15
Shuntaro Ogura, Kaori Kurata, Yuki Hattori, Hiroshi Takase, Toshina Ishiguro-Oonuma, Yoonha Hwang, Soyeon Ahn, Inwon Park, Wataru Ikeda, Sentaro Kusuhara, Yoko Fukushima, Hiromi Nara, Hideto Sakai, Takashi Fujiwara, Jun Matsushita, Masatsugu Ema, Masanori Hirashima, Takashi Minami, Masabumi Shibuya, Nobuyuki Takakura, Pilhan Kim, Takaki Miyata, Yuichiro Ogura, Akiyoshi Uemura
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28188224/lung-pericyte-like-cells-are-functional-interstitial-immune-sentinel-cells
#16
Chi F Hung, Kristen L Mittelsteadt, Rena Brauer, Bonnie L McKinney, Teal S Hallstrand, William C Parks, Peter Chen, Lynn M Schnapp, W Conrad Liles, Jeremy S Duffield, William A Altemeier
Pericytes are perivascular PDGF receptor-β(+) (PDGFRβ(+)) stromal cells required for vasculogenesis and maintenance of microvascular homeostasis in many organs. Because of their unique juxtaposition to microvascular endothelium, lung PDGFRβ(+) cells are well situated to detect proinflammatory molecules released following epithelial injury and promote acute inflammatory responses. Thus we hypothesized that these cells represent an unrecognized immune surveillance or injury-sentinel interstitial cell. To evaluate this hypothesis, we isolated PDGFRβ(+) cells from murine lung and demonstrated that they have characteristics consistent with a pericyte population (referred to as pericyte-like cells for simplicity hereafter)...
April 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28183292/case-report-rapid-and-durable-response-to-pdgfr-targeted-therapy-in-a-child-with-refractory-multiple-infantile-myofibromatosis-and-a-heterozygous-germline-mutation-of-the-pdgfrb-gene
#17
Peter Mudry, Ondrej Slaby, Jakub Neradil, Jana Soukalova, Kristyna Melicharkova, Ondrej Rohleder, Marta Jezova, Anna Seehofnerova, Elleni Michu, Renata Veselska, Jaroslav Sterba
BACKGROUND: Infantile myofibromatosis belongs to a family of soft tissue tumors. The majority of these tumors have benign behavior but resistant and malignant courses are known, namely in tumors with visceral involvement. The standard of care is surgical resection. Observations suggest that low dose chemotherapy is beneficial. The treatment of resistant or relapsed patients with multifocal disease remains challenging. Patients that harbor an actionable mutation in the kinase domain are potential subjects for targeted tyrosine kinase inhibitor therapy...
February 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28170170/the-infrapatellar-fat-pad-as-a-source-of-perivascular-stem-cells-with-increased-chondrogenic-potential-for-regenerative-medicine
#18
Paul Hindle, Nusrat Khan, Leela Biant, Bruno Péault
Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have demonstrated increased chondrogenic potential compared with those from subcutaneous fat. This research assessed the chondrogenic potential of IFP PSCs compared with MSCs from the IFP and bone marrow...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28148739/multiple-routes-of-pdgfr%C3%AE-endocytosis
#19
(no author information available yet)
No abstract text is available yet for this article.
February 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28139736/young-bone-marrow-sca-1-stem-cells-rejuvenate-the-aged-heart-and-improve-function-after-injury-through-pdgfr%C3%AE-akt-pathway
#20
Shu-Hong Li, Lu Sun, Lei Yang, Jiao Li, Zhengbo Shao, Guo-Qing Du, Jun Wu, Richard D Weisel, Ren-Ke Li
Bone marrow (BM) reconstitution with young BM cells in aged recipients restores the functionality of cardiac resident BM-derived progenitors. This study investigated the cell type primarily responsible for this effect. We reconstituted old mice with BM cells from young or old mice and found that the number of stem cell antigen 1 (Sca-1) cells homing to the heart was significantly greater in young than old chimeras. We then reconstituted old mice with young BM Sca-1(+) or Sca-1(-) cells. We found that Sca-1 cells repopulated the recipient BM and homed to the heart...
January 31, 2017: Scientific Reports
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