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https://www.readbyqxmd.com/read/29885791/markers-for-human-brain-pericytes-and-smooth-muscle-cells
#1
Leon C D Smyth, Justin Rustenhoven, Emma L Scotter, Patrick Schweder, Richard L M Faull, Thomas I H Park, Mike Dragunow
Brain pericytes and vascular smooth muscle cells (vSMCs) are a critical component of the neurovascular unit and are important in regulating cerebral blood flow and blood-brain barrier integrity. Identification of subtypes of mural cells in tissue and in vitro is important to any study of their function, therefore we identified distinct mural cell morphologies in neurologically normal post-mortem human brain. Further, the distribution of mural cell markers platelet-derived growth factor receptor-β (PDGFRβ), α-smooth muscle actin (αSMA), CD13, neural/glial antigen-2 (NG2), CD146 and desmin was examined...
June 7, 2018: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29875766/complement-activation-during-ischemia-reperfusion-injury-induces-pericyte-to-myofibroblast-transdifferentiation-regulating-peritubular-capillary-lumen-reduction-through-perk-signaling
#2
Giuseppe Castellano, Rossana Franzin, Alessandra Stasi, Chiara Divella, Fabio Sallustio, Paola Pontrelli, Giuseppe Lucarelli, Michele Battaglia, Francesco Staffieri, Antonio Crovace, Giovanni Stallone, Marc Seelen, Mohamed R Daha, Giuseppe Grandaliano, Loreto Gesualdo
Pericytes are one of the principal sources of scar-forming myofibroblasts in chronic kidneys disease. However, the modulation of pericyte-to-myofibroblast transdifferentiation (PMT) in the early phases of acute kidney injury is poorly understood. Here, we investigated the role of complement in inducing PMT after transplantation. Using a swine model of renal ischemia/reperfusion (I/R) injury, we found the occurrence of PMT after 24 h of I/R injury as demonstrated by reduction of PDGFRβ+ /NG2+ cells with increase in myofibroblasts marker αSMA...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29869048/platelet-derived-growth-factor-subunit-b-signaling-promotes-pericyte-migration-in-response-to-loud-sound-in-the-cochlear-stria-vascularis
#3
Zhiqiang Hou, Xiaohan Wang, Jing Cai, Jinhui Zhang, Ahmed Hassan, Manfred Auer, Xiaorui Shi
Normal blood supply to the cochlea is critical for hearing. Noise damages auditory sensory cells and has a marked effect on the microvasculature in the cochlear lateral wall. Pericytes in the stria vascularis (strial pericytes) are particularly vulnerable and sensitive to acoustic trauma. Exposure of NG2DsRedBAC transgenic mice (6-8 weeks old) to wide-band noise at a level of 120 dB for 3 h per day for 2 consecutive days produced a significant hearing threshold shift and caused pericytes to protrude and migrate from their normal endothelial attachment sites...
June 4, 2018: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/29845424/the-histone-deacetylases-hdac1-and-hdac2-are-required-for-the-growth-and-survival-of-renal-carcinoma-cells
#4
Nicole Kiweler, Boris Brill, Matthias Wirth, Ines Breuksch, Teresa Laguna, Cornelia Dietrich, Susanne Strand, Günter Schneider, Bernd Groner, Falk Butter, Thorsten Heinzel, Walburgis Brenner, Oliver H Krämer
Novel therapies are required for the treatment of metastatic renal cell carcinoma (RCC), which is associated with inoperable disease and patient death. Histone deacetylases (HDACs) are epigenetic modifiers and potential drug targets. Additional information on molecular pathways that are altered by histone deacetylase inhibitors (HDACi) in RCC cells is warranted. It should equally be delineated further which individual members of the 18 mammalian HDACs determine the survival and tumor-associated gene expression programs of such cells...
May 29, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29813125/role-of-integrin-alpha8-in-murine-model-of-lung-fibrosis
#5
Chi F Hung, Carole L Wilson, Yu-Hua Chow, Lynn M Schnapp
BACKGROUND: Integrin α8 (ITGA8) heterodimerizes with integrin β1 and is highly expressed in stromal cells of the lung. Platelet-derived growth factor receptor beta (PDGFRβ+) cells constitute a major population of contractile myofibroblasts in the lung following bleomycin-induced fibrosis. Integrin α8β1 is upregulated in fibrotic foci in bleomycin-induced lung injury. However, the functional role of ITGA8 in fibrogenesis has not been characterized. In this study, we examined whether genetic deletion of ITGA8 from PDGFRβ+ cells in the lung altered fibrosis...
2018: PloS One
https://www.readbyqxmd.com/read/29799521/heat-shock-factor-1-confers-resistance-to-lapatinib-in-erbb2-positive-breast-cancer-cells
#6
Alisha Yallowitz, Amr Ghaleb, Lucas Garcia, Evguenia M Alexandrova, Natalia Marchenko
Despite success of ERBB2-targeted therapies such as lapatinib, resistance remains a major clinical concern. Multiple compensatory receptor tyrosine kinase (RTK) pathways are known to contribute to lapatinib resistance. The heterogeneity of these adaptive responses is a significant hurdle for finding most effective combinatorial treatments. The goal of this study was to identify a unifying molecular mechanism whose targeting could help prevent and/or overcome lapatinib resistance. Using the MMTV-ERBB2;mutant p53 (R175H) in vivo mouse model of ERBB2-positive breast cancer, together with mouse and human cell lines, we compared lapatinib-resistant vs...
May 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29792166/the-pdgfr%C3%AE-erk1-2-pathway-regulates-cdcp1-expression-in-triple-negative-breast-cancer
#7
Luca Forte, Federica Turdo, Cristina Ghirelli, Piera Aiello, Patrizia Casalini, Marilena Valeria Iorio, Elvira D'Ippolito, Patrizia Gasparini, Roberto Agresti, Beatrice Belmonte, Gabriella Sozzi, Lucia Sfondrini, Elda Tagliabue, Manuela Campiglio, Francesca Bianchi
BACKGROUND: CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. METHODS: The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29771991/progenitor-renin-lineage-cells-are-not-involved-in-the-regeneration-of-glomerular-endothelial-cells-during-experimental-renal-thrombotic-microangiopathy
#8
Leo Ruhnke, Jan Sradnick, Moath Al-Mekhlafi, Michael Gerlach, Florian Gembardt, Bernd Hohenstein, Vladimir T Todorov, Christian Hugo
Endothelial cells (EC) frequently undergo primary or secondary injury during kidney disease such as thrombotic microangiopathy or glomerulonephritis. Renin Lineage Cells (RLCs) serve as a progenitor cell niche after glomerular damage in the adult kidney. However, it is not clear whether RLCs also contribute to endothelial replenishment in the glomerulus following endothelial injury. Therefore, we investigated the role of RLCs as a potential progenitor niche for glomerular endothelial regeneration. We used an inducible tet-on triple-transgenic reporter strain mRen-rtTAm2/LC1/LacZ to pulse-label the renin-producing RLCs in adult mice...
2018: PloS One
https://www.readbyqxmd.com/read/29771332/mechanisms-of-skeletal-muscle-wasting-in-a-mouse-model-for-myotonic-dystrophy-type-1
#9
Ginny R Morriss, Kimal Rajapakshe, Shixia Huang, Cristian Coarfa, Thomas A Cooper
Myotonic dystrophy type 1 (DM1) is a multisystemic disease resulting in severe muscle weakening and wasting. DM1 is caused by expansion of CTG repeats in the 3'-UTR of the DMPK gene. We have developed an inducible, skeletal muscle-specific mouse model of DM1 (CUG960) that expresses 960 CUG repeats in the context of human DMPK exons 11-15. CUG960 RNA-expressing mice induced at PN1, as well as adult-onset animals, show clear, measurable muscle wasting accompanied by severe histological defects including central myonuclei, reduced fiber cross sectional area, increased percentage of oxidative myofibers, and the presence of nuclear RNA foci that colocalize with Mbnl1 protein...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29738888/effect-of-pdgf-b-aptamer-on-pdgfr%C3%AE-pdgf-b-interaction-molecular-dynamics-study
#10
Cong Quang Vu, Pichayanoot Rotkrua, Boonchoy Soontornworajit, Yuthana Tantirungrotechai
PDGFRβ/PDGF-B interaction plays a role in angiogenesis, and is mandatory in wound healing and cancer treatment. It has been reported that the PDGF-B aptamer was able to bind to PDGF-B, thus regulating the angiogenesis. However, the binding interaction between the aptamer and the growth factor, including the binding sites, has not been well investigated. This study applied a molecular dynamics (MD) simulation to investigate the aptamer-growth factor interaction in the presence or absence of a receptor (PDGFRβ)...
June 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29724654/the-novel-pathogenesis-of-retinopathy-mediated-by-multiple-rtk-signals-is-uncovered-in-newly-developed-mouse-model
#11
Hideyuki Kitahara, Sayaka Kajikawa, Yoko Ishii, Seiji Yamamoto, Takeru Hamashima, Erika Azuma, Hikari Sato, Takako Matsushima, Masabumi Shibuya, Yutaka Shimada, Masakiyo Sasahara
Pericyte desorption from retinal blood vessels and subsequent vascular abnormalities are the pathogenesis of diabetic retinopathy (DR). Although the involvement of abnormal signals including platelet-derived growth factor receptor-β (PDGFRβ) and vascular endothelial growth factor-A (VEGF-A) have been hypothesized in DR, the mechanisms that underlie this processes are largely unknown. Here, novel retinopathy mouse model (N-PRβ-KO) was developed with conditional Pdgfrb gene deletion by Nestin promoter-driven Cre recombinase (Nestin-Cre) consistently reproduced through early non-proliferative to late proliferative DR pathologies...
April 25, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29704660/genetic-and-epigenetic-control-of-adipose-development
#12
REVIEW
Olga Gulyaeva, Jon Dempersmier, Hei Sook Sul
White adipose tissue (WAT) is the primary energy storage organ and its excess contributes to obesity, while brown adipose tissue (BAT) and inducible thermogenic (beige/brite) adipocytes in WAT dissipate energy via Ucp1 to maintain body temperature. BAT and subcutaneous WAT develop perinatally while visceral WAT forms after birth from precursors expressing distinct markers, such as Myf5, Pref-1, Wt1, and Prx1, depending on the anatomical location. In addition to the embryonic adipose precursors, a pool of endothelial cells or mural cells expressing Pparγ, Pdgfrβ, Sma and Zfp423 may become adipocytes during WAT expansion in adults...
April 25, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29679460/limbal-niche-cells-are-a-potent-resource-of-adult-mesenchymal-progenitors
#13
REVIEW
Ping Guo, Hong Sun, Yuan Zhang, Sean Tighe, Shuangling Chen, Chen-Wei Su, Yongsong Liu, Hongxia Zhao, Min Hu, Yingting Zhu
Limbal niche cells located in the limbal Palisades of Vogt are mesenchymal stem cells that reside next to limbal basal epithelial cells. Limbal niche cells are progenitors that express embryonic stem cell markers such as Nanog, Nestin, Oct4, Rex1, Sox2 and SSEA4, mesenchymal cell markers such as CD73, CD90 and CD105, and angiogenesis markers such as Flk-1, CD31, CD34, VWF, PDGFRβ and α-SMA, but negative for CD45. In addition, the stemness of limbal niche cells can be maintained during their cell culture in a three-dimension environment...
April 20, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29667914/inactivation-of-map3k7-in-foxd1-expressing-cells-results-in-loss-of-mesangial-pdgfr%C3%AE-and-juvenile-kidney-scarring
#14
Michele J Karolak, Justin A Guay, Leif Oxburgh
Transforming growth factor beta (TGFβ) plays a central role in renal scarring, controlling extracellular matrix deposition by interstitial cells and mesangial cells. TGFβ signals through Smad and mitogen activated protein kinase (MAPK) pathways. To understand the role of MAPK in interstitial and mesangial cells, we genetically inactivated TGFβ-activated kinase 1 (Map3k7) using Foxd1+/cre. Embryonic kidney development was unperturbed in mutants, but spontaneous scarring of the kidney ensued during the first postnatal week, with retention of embryonic nephrogenic rests and accumulation of collagen IV in the mesangium...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29665322/tumour-cell-expression-of-interleukin-6-receptor-%C3%AE-is-associated-with-response-rates-in-patients-treated-with-sunitinib-for-metastatic-clear-cell-renal-cell-carcinoma
#15
Martin Pilskog, Leif Bostad, Reidunn J Edelmann, Lars A Akslen, Christian Beisland, Oddbjørn Straume
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, and anti-angiogenic treatment is currently first line therapy for metastatic ccRCC (mccRCC). Response rates and duration of response show considerable variation, and adverse events have a major influence on patient quality of life. The need for predictive biomarkers to select responders to receptor tyrosine kinase inhibitors upfront is urgent. We investigated the predictive value of immunohistochemical biomarkers associated with angiogenesis and systemic inflammation in mccRCC...
April 2018: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/29627438/perivascular-cell-%C3%AE-v-integrins-as-a-target-to-treat-skeletal-muscle-fibrosis
#16
Pedro H D M Prazeres, Anaelise O M Turquetti, Patrick O Azevedo, Rodrigo S N Barreto, Maria A Miglino, Akiva Mintz, Osvaldo Delbono, Alexander Birbrair
Fibrosis following injury leads to aberrant regeneration and incomplete functional recovery of skeletal muscle, but the lack of detailed knowledge about the cellular and molecular mechanisms involved hampers the design of effective treatments. Using state-of-the-art technologies, Murray et al. (2017) found that perivascular PDGFRβ-expressing cells generate fibrotic cells in the skeletal muscle. Strikingly, genetic deletion of αv integrins from perivascular PDGFRβ-expressing cells significantly inhibited skeletal muscle fibrosis without affecting muscle vascularization or regeneration...
June 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29592879/itraconazole-induced-inhibition-on-human-esophageal-cancer-cell-growth-requires-ampk-activation
#17
Min-Bin Chen, Yuan-Yuan Liu, Zhao-Yu Xing, Zhi-Qing Zhang, Qin Jiang, Pei-Hua Lu, Cong Cao
We here evaluated the antiesophageal cancer cell activity by the antifungal drug itraconazole. Our results show that μg/mL concentrations of itraconazole potently inhibited survival and proliferation of established (TE-1 and Eca-109) and primary human esophageal cancer cells. Itraconazole activated AMPK signaling, which was required for subsequent esophageal cancer cell death. Pharmacologic AMPK inhibition, AMPKα1 shRNA, or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells...
June 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29592525/meis1-is-specifically-upregulated-in-kidney-myofibroblasts-during-aging-and-injury-but-is-not-required-for-kidney-homeostasis-or-fibrotic-response
#18
Monica Chang-Panesso, Farid F Kadyrov, Flavia G Machado, Ashish Kumar, Benjamin D Humphreys
The homeobox transcription factor Meis1 is required for mammalian development and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease, and tested this using cell lineage tracing and cell specific Meis1 deletion in development, aging and fibrotic disease. We observed strong expression of Meis1 in PDGFRβ positive pericytes and perivascular fibroblasts, both in adult mouse and to a lesser degree in human kidney...
March 28, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29578538/combinatorial-inhibition-of-ptpn12-regulated-receptors-leads-to-a-broadly-effective-therapeutic-strategy-in-triple-negative-breast-cancer
#19
Amritha Nair, Hsiang-Ching Chung, Tingting Sun, Siddhartha Tyagi, Lacey E Dobrolecki, Rocio Dominguez-Vidana, Sarah J Kurley, Mayra Orellana, Alexander Renwick, David M Henke, Panagiotis Katsonis, Earlene Schmitt, Doug W Chan, Hui Li, Sufeng Mao, Ivana Petrovic, Chad J Creighton, Carolina Gutierrez, Julien Dubrulle, Fabio Stossi, Jeffrey W Tyner, Olivier Lichtarge, Charles Y Lin, Bing Zhang, Kenneth L Scott, Susan G Hilsenbeck, Jinpeng Sun, Xiao Yu, C Kent Osborne, Rachel Schiff, James G Christensen, David J Shields, Mothaffar F Rimawi, Matthew J Ellis, Chad A Shaw, Michael T Lewis, Thomas F Westbrook
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer diagnosed in more than 200,000 women each year and is recalcitrant to targeted therapies. Although TNBCs harbor multiple hyperactive receptor tyrosine kinases (RTKs), RTK inhibitors have been largely ineffective in TNBC patients thus far. We developed a broadly effective therapeutic strategy for TNBC that is based on combined inhibition of receptors that share the negative regulator PTPN12. Previously, we and others identified the tyrosine phosphatase PTPN12 as a tumor suppressor that is frequently inactivated in TNBC...
May 2018: Nature Medicine
https://www.readbyqxmd.com/read/29571051/substrate-stiffness-modulates-the-multipotency-of-human-neural-crest-derived-ectomesenchymal-stem-cells-via-cd44-mediated-pdgfr-signaling
#20
Akshaya Srinivasan, Shu-Yung Chang, Shipin Zhang, Wei Seong Toh, Yi-Chin Toh
Mesenchymal stem cells (MSCs) have been isolated from various mesodermal and ectodermal tissues. While the phenotypic and functional heterogeneity of MSCs stemming from their developmental origins has been acknowledged, the genetic and environmental factors underpinning these differences are not well-understood. Here, we investigated whether substrate stiffness mediated mechanical cues can directly modulate the development of ectodermal MSCs (eMSCs) from a precursor human neural crest stem cell (NCSC) population...
June 2018: Biomaterials
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