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https://www.readbyqxmd.com/read/28649987/a-ppar%C3%AE-transcriptional-cascade-directs-adipose-progenitor-cell-niche-interaction-and-niche-expansion
#1
Yuwei Jiang, Daniel C Berry, Ayoung Jo, Wei Tang, Robert W Arpke, Michael Kyba, Jonathan M Graff
Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels. Yet, the signals and mechanisms that govern adipose vascular niche formation and APC niche interaction are unknown. Here we show that the assembly and maintenance of the adipose vascular niche is controlled by PPARγ acting within APCs. PPARγ triggers a molecular hierarchy that induces vascular sprouting, APC vessel niche affinity and APC vessel occupancy. Mechanistically, PPARγ transcriptionally activates PDGFRβ and VEGF...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634350/a-subset-of-cerebrovascular-pericytes-originates-from-mature-macrophages-in-the-very-early-phase-of-vascular-development-in-cns
#2
Seiji Yamamoto, Masashi Muramatsu, Erika Azuma, Masashi Ikutani, Yoshinori Nagai, Hiroshi Sagara, Bon-Nyeo Koo, Satomi Kita, Erin O'Donnell, Tsuyoshi Osawa, Hiroyuki Takahashi, Ken-Ichi Takano, Mitsuko Dohmoto, Michiya Sugimori, Isao Usui, Yasuhide Watanabe, Noboru Hatakeyama, Takahiro Iwamoto, Issei Komuro, Kiyoshi Takatsu, Kazuyuki Tobe, Shumpei Niida, Naoyuki Matsuda, Masabumi Shibuya, Masakiyo Sasahara
Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31(+)F4/80(+) hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627746/hepatic-perivascular-mesenchymal-stem-cells-with-myogenic-properties
#3
Sudheer Shenoy P, Bipasha Bose
Pericytes are multipotent mesenchymal stem cells (MSCs) located on the walls of blood vessels in various organs and are characterized as CD146(+) cells.. In this study, we have first immunohistochemically detected such pericytes in the perivascular regions of liver from two mouse genotypes namely wild-type (WT) and myostatin null (Mstn(-/-) ). We further isolated such pericytes using sorting as CD146(+) CD34(-) CD56(-) CD45(-) cells. The main finding of this study involve the contrasting -fibrogenic versus myogenic behavior of liver pericytes from WTMstn(-/-) ) mouse respectively...
June 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28610597/anti-connective-tissue-growth-factor-ctgf-ccn2-monoclonal-antibody-attenuates-skin-fibrosis-in-mice-models-of-systemic-sclerosis
#4
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Kenneth E Lipson, Andrew Leask, Maria Trojanowska
BACKGROUND: Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CTGF blockade in a preclinical model of SSc using two approaches: smooth muscle cell fibroblast-specific deletion of CTGF (CTGF knockout (KO)) or a human anti-CTGF monoclonal antibody, FG-3019...
June 13, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28605361/isolation-of-type-i-and-type-ii-pericytes-from-mouse-skeletal-muscles
#5
Abhijit Nirwane, Jyoti Gautam, Yao Yao
Pericytes are perivascular multipotent cells that show heterogeneity in different organs or even within the same tissue. In skeletal muscles, there are at least two pericyte subpopulations (called type I and type II), which express different molecular markers and have distinct differentiation capabilities. Using NG2-DsRed and Nestin-GFP double-transgenic mice, type I (NG2-DsRed(+)Nestin-GFP(-)) and type II (NG2-DsRed(+)Nestin-GFP(+)) pericytes have been successfully isolated. However, the availability of these double-transgenic mice prevents the widespread use of this purification method...
May 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28588623/angiogenic-capacity-of-dental-pulp-stem-cell-regulated-by-sdf-1%C3%AE-cxcr4-axis
#6
Hyun Nam, Gee-Hye Kim, Yoon-Kyung Bae, Da-Eun Jeong, Kyeung-Min Joo, Kyunghoon Lee, Sun-Ho Lee
Previously, the perivascular characteristics of dental pulp stem cells (DPSCs) were reported, which suggested the potential application of DPSCs as perivascular cell source. In this study, we investigated whether DPSCs had angiogenic capacity by coinjection with human umbilical vein endothelial cells (HUVECs) in vivo; in addition, we determined the role of stromal cell-derived factor 1-α (SDF-1α) and C-X-C chemokine receptor type 4 (CXCR4) axis in the mutual interaction between DPSCs and HUVECs. Primarily isolated DPSCs showed mesenchymal stem cell- (MSC-) like characteristics...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28578517/phosphate-transporters-expression-in-patients-with-primary-familial-brain-calcifications
#7
L F Pimentel, R R Lemos, J R Oliveira
Primary familial brain calcification (PFBC), formerly known as Fahr disease, is a rare neurological disorder characterized by extensive calcification deposits in the brain. So far, four genes have been reported with variations associated with PFBC, SLC20A2, PDGFβ, PDGFRβ, and XPR1. Using real-time qPCR, we analyzed the expression of three inorganic phosphate (Pi) transporters (SLC20A1, SLC20A2, and XPR1) in patients with PFBC. Our results showed a significant reduction (~40%) of SLC20A2 expression in the patients carrying mutation whereas no significant change was observed within the patients without known mutations...
June 3, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28567229/platelet-derived-growth-factor-receptor-positive-pericytic-cells-of-white-adipose-tissue-from-critical-limb-ischemia-patients-display-mesenchymal-stem-cell-like-properties
#8
Eo Jin Kim, Sang Gyo Seo, Hyuk Soo Shin, Doo Jae Lee, Ji Hye Kim, Dong Yeon Lee
BACKGROUND: The pericytes in the blood vessel wall have recently been identified to be important in regulating vascular formation, stabilization, remodeling, and function. We isolated and identified pericyte-like platelet-derived growth factor receptor beta-positive (PDGFRβ+) cells from the stromal vascular fraction (SVF) of adipose tissue from critical limb ischemia (CLI) patients and investigated their potential as a reliable source of stem cells for cell-based therapy. METHODS: De-identified subcutaneous fat tissues were harvested after amputation in CLI patients...
June 2017: Clinics in Orthopedic Surgery
https://www.readbyqxmd.com/read/28564607/specification-and-diversification-of-pericytes-and-smooth-muscle-cells-from-mesenchymoangioblasts
#9
Akhilesh Kumar, Saritha Sandra D'Souza, Oleg V Moskvin, Huishi Toh, Bowen Wang, Jue Zhang, Scott Swanson, Lian-Wang Guo, James A Thomson, Igor I Slukvin
Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ(+)CD271(+)CD73(-) mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28561780/synthesis-and-evaluation-of-novel-2-pyrrolidone-fused-2-oxoindolin-3-ylidene-methylpyrrole-derivatives-as-potential-multi-target-tyrosine-kinase-receptor-inhibitors
#10
Ting-Hsuan Yang, Chun-I Lee, Wen-Hsin Huang, An-Rong Lee
Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. The target compounds were obtained by condensation of 5-substituted oxindoles with N-substituted 2-pyrrolidone aldehyde 7 in satisfactory yields. Of these, 11 and 12 had the highest potency and, compared to sunitinib, showed: (1) significant increase in anti-proliferation of various cancer cells with a favorable selective index (SI); (2) higher inhibitory potency against both VEGFR-2 and PDGFRβ...
May 31, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28558791/receptor-tyrosine-kinases-play-a-significant-role-in-human-oligodendrocyte-inflammation-and-cell-death-associated-with-the-lyme-disease-bacterium-borrelia-burgdorferi
#11
Geetha Parthasarathy, Mario T Philipp
BACKGROUND: In previous studies, human oligodendrocytes were demonstrated to undergo apoptosis in the presence of Borrelia burgdorferi under an inflammatory milieu. Subsequently, we determined that the MEK/ERK pathway played a significant role in triggering downstream inflammation as well as apoptosis. However, the identity of receptors triggered by exposure to B. burgdorferi and initiating signaling events was unknown. METHODS: In this study, we explored the role of several TLR and EGFR/FGFR/PDGFR tyrosine kinase pathways in inducing inflammation in the presence of B...
May 30, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28553358/inhibition-of-lysyl-oxidases-impairs-migration-and-angiogenic-properties-of-tumor-associated-pericytes
#12
Aline Lopes Ribeiro, Carolini Kaid, Patrícia B G Silva, Beatriz A Cortez, Oswaldo Keith Okamoto
Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28548933/kir2dl5-mutation-and-loss-underlies-sporadic-dermal-neurofibroma-pathogenesis-and-growth
#13
Corina Anastasaki, Sonika Dahiya, David H Gutmann
Dermal neurofibromas (DNFs) are benign peripheral nerve sheath tumors thought to originate from Schwann cell progenitors. These tumors represent one of the hallmarks of the neurofibromatosis type 1 (NF1) tumor predisposition syndrome, where they can number in the thousands. While NF1-DNFs arise due to mutations in the NF1 gene, the vast majority of DNFs occur sporadically (sp-DNFs), where the genetic etiology is currently unknown. Herein, we employed whole-exome sequencing of sp-DNFs to identify a recurrent mutation in the KIR2DL5 gene, which codes for a protein suppressor of natural killer (NK) cell activity...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536901/increased-epithelial-free-areas-in-thymuses-with-altered-ephb-mediated-thymocyte-thymic-epithelial-cell-interactions
#14
Javier García-Ceca, Sara Montero-Herradón, David Alfaro, Agustín G Zapata
Epithelial-free areas, present in both thymic cortex and medulla, have been studied in WT and EphB-deficient mice that have important alterations in the development of thymic epithelium due to the lack of proper thymocyte-thymic epithelial cell interactions. In both WT and mutant thymuses, the number and size of epithelial-free areas are significantly larger in the medulla than in the cortex. The two parameters show a reverse correlation: low numbers of these areas course with large epithelial-free areas and vice versa...
May 24, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28534507/cecr1-mediated-cross-talk-between-macrophages-and-vascular-mural-cells-promotes-neovascularization-in-malignant-glioma
#15
C Zhu, I Chrifi, D Mustafa, M van der Weiden, P J M Leenen, D J Duncker, J M Kros, C Cheng
Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28531107/analysis-of-gene-expression-signatures-in-cancer-associated-stroma-from-canine-mammary-tumours-reveals-molecular-homology-to-human-breast-carcinomas
#16
Julia Ettlin, Elena Clementi, Parisa Amini, Alexandra Malbon, Enni Markkanen
Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28526409/expression-and-purification-of-functional-pdgf-receptor-beta
#17
Qingbin Shang, Liang Zhao, Xiaojing Wang, Meimei Wang, Sen-Fang Sui, Li-Zhi Mi
Platelet Derived Growth Factor receptors (PDGFRs), members of receptor tyrosine kinase superfamily, play essential roles in early hematopoiesis, angiogenesis and organ development. Dysregulation of PDGF receptor signaling under pathological conditions associates with cancers, vascular diseases, and fibrotic diseases. Therefore, they are attractive targets in drug development. Like any other membrane proteins with a single-pass transmembrane domain, the high-resolution structural information of the full-length PDGF receptors is still not resolved...
July 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#18
Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman
BACKGROUND: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. RESULTS: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28508859/plastic-roles-of-pericytes-in-the-blood-retinal-barrier
#19
Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H Adams, Gou Young Koh
The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28506734/mtor-vegf-pdgfr-and-c-kit-signaling-pathway-activation-in-kaposi-sarcoma
#20
Darcy A Kerr, Satya Vara Prasad Busarla, Devon C Gimbel, Aliyah R Sohani, Rosalynn M Nazarian
Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (n=274), most (90%) associated with human immunodeficiency virus (HIV)...
May 12, 2017: Human Pathology
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