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https://www.readbyqxmd.com/read/28220032/pharmacologic-blockade-of-%C3%AE-v%C3%AE-1-integrin-ameliorates-renal-failure-and-fibrosis-in-vivo
#1
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
#2
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...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#3
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-immune-sentinel-cells
#4
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 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 pro-inflammatory 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)...
February 10, 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
#5
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
#6
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
#7
(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
#8
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
https://www.readbyqxmd.com/read/28138400/high-expression-of-stromal-pdgfr%C3%AE-is-associated-with-reduced-benefit-of-tamoxifen-in-breast-cancer
#9
Janna Paulsson, Lisa Rydén, Carina Strell, Oliver Frings, Nicholas P Tobin, Tommy Fornander, Jonas Bergh, Göran Landberg, Olle Stål, Arne Östman
Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFRβ is an important regulator of fibroblasts. Experimental studies have linked PDGFRβ-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFRβ-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28122789/pdgfr%C3%AE-regulates-adipose-tissue-expansion-and-glucose-metabolism-via-vascular-remodeling-in-diet-induced-obesity
#10
Yasuhiro Onogi, Tsutomu Wada, Chie Kamiya, Kento Inata, Takatoshi Matsuzawa, Yuka Inaba, Kumi Kimura, Hiroshi Inoue, Seiji Yamamoto, Yoko Ishii, Daisuke Koya, Hiroshi Tsuneki, Masakiyo Sasahara, Toshiyasu Sasaoka
Platelet-derived growth factor (PDGF) is a key factor of angiogenesis; however, its role in adult obesity remains unclear. In order to clarify its pathophysiological role, we investigated the significance of a PDGF receptor β on adipose tissue expansion and glucose metabolism. Mature vessels in the epididymal white adipose tissue (eWAT) were tightly wrapped with pericytes in normal mice. Pericytes desorption from vessels and the subsequent proliferations of endothelial cells were markedly increased in the eWAT of diet-induced obese mice...
January 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28114800/pre-treatment-of-human-mesenchymal-stem-cells-with-inflammatory-factors-or-hypoxia-does-not-influence-migration-to-osteoarthritic-cartilage-and-synovium
#11
Maarten J C Leijs, Gerben M van Buul, Jan A N Verhaar, Martin J Hoogduijn, Pieter K Bos, Gerjo J V M van Osch
BACKGROUND: Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. HYPOTHESIS: Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. STUDY DESIGN: Controlled laboratory study. METHODS: We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors...
January 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28109944/synthesis-biological-evaluation-and-molecular-dynamics-md-simulation-studies-of-three-novel-f-18-labeled-and-focal-adhesion-kinase-fak-targeted-5-bromo-pyrimidines-as-radiotracers-for-tumor
#12
Yu Fang, Dawei Wang, Xingyu Xu, Jianping Liu, Aiqin Wu, Xiang Li, Qianqian Xue, Huan Wang, Hang Wang, Huabei Zhang
Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N(2)-(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N(4)-(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC50 in the range of 91...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28102844/human-adipose-stem-cell-differentiation-is-highly-affected-by-cancer-cells-both-in-vitro-and-in-vivo-implication-for-autologous-fat-grafting
#13
Francesca Paino, Marcella La Noce, Diego Di Nucci, Giovanni Francesco Nicoletti, Rosa Salzillo, Alfredo De Rosa, Giuseppe Andrea Ferraro, Gianpaolo Papaccio, Vincenzo Desiderio, Virginia Tirino
Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour progression, raising some concerns regarding their use in regenerative medicine. In this context, we co-cultured either SAOS2 osteosarcoma or MCF7 breast cancer cells with human adipose stem cells (hASCs), in order to evaluate potential effects of cancer cells on hASCs differentiation, in vitro and in vivo. In this study we observed that both SAOS2 and MCF7 cell lines induced an increase in hASCs proliferation, compared to hASCs alone, but, surprisingly, neither changes in the expression of CD90, CD29, CD324 and vimentin, nor variations in the Twist and Slug mRNAs were detectable...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28100839/tyrosine-kinase-blocking-collagen-iv-derived-peptide-suppresses-ocular-neovascularization-and-vascular-leakage
#14
Raquel Lima E Silva, Yogita Kanan, Adam C Mirando, Jayoung Kim, Ron B Shmueli, Valeria E Lorenc, Seth D Fortmann, Jason Sciamanna, Niranjan B Pandey, Jordan J Green, Aleksander S Popel, Peter A Campochiaro
Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefit in several retinal and choroidal vascular diseases, but some patients still experience suboptimal outcomes, and the need for frequent intraocular injections is a barrier to good outcomes. A mimetic peptide derived from collagen IV, AXT107, suppressed subretinal neovascularization (NV) in two mouse models predictive of effects in neovascular age-related macular degeneration (NVAMD) and inhibited retinal NV in a model predictive of effects in ischemic retinopathies...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28052876/pericyte-and-immune-cells-contribute-to-complement-activation-in-tubulointerstitial-fibrosis
#15
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
#16
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
#17
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
#18
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...
February 1, 2017: 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
#19
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
#20
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
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