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https://www.readbyqxmd.com/read/29679460/limbal-niche-cells-are-a-potent-resource-of-adult-mesenchymal-progenitors
#1
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
#2
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
#3
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
#4
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...
April 5, 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
#5
Min-Bin Chen, Yuan-Yuan Liu, Zhao-Yu Xing, Zhi-Qing Zhang, Qin Jiang, Pei-Hua Lu, Cong Cao
We here evaluated the anti-esophageal 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 AMP-activated protein kinase (AMPK) signaling, which was required for subsequent esophageal cancer cell death. Pharmacological AMPK inhibition, AMPKα1 shRNA or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells...
March 28, 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
#6
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
#7
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...
March 26, 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
#8
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...
March 14, 2018: Biomaterials
https://www.readbyqxmd.com/read/29558627/pdgf-bb-and-tgf%C3%AE-mediated-cellular-crosstalk-during-hepatic-injury-activates-hepatic-stellate-cells
#9
Sowmya Mekala, Subbarao V Tullimilli, Ramasatyaveni Geesala, Kanakaraju Manupati, Neha R Dhoke, Amitava Das
Apoptotic hepatocytes release factors that activate Hepatic Stellate Cells (HSCs) thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride or thioacetamide. Hepatotoxicant-induced diseased hepatic tissue histology correlated with a differential expression of fibrosis-related genes. Marked increase in co-staining of TGFRIIβ-Desmin or α-SMA-PDGFRβ, markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V-Cytokeratin expressing hepatocytes...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29555579/analysis-of-cancer-associated-fibroblasts-and-the-epithelial-mesenchymal-transition-in-cutaneous-basal-cell-carcinoma-squamous-cell-carcinoma-and-malignant-melanoma
#10
Kousuke Sasaki, Tamotsu Sugai, Kazuyuki Ishida, Mitsumasa Osakabe, Hiroo Amano, Hiroaki Kimura, Minoru Sakuraba, Katsuhiko Kashiwa, Seiichiro Kobayashi
Activated cancer-associated fibroblasts (CAFs) and fibroblasts that have undergone the epithelial-mesenchymal transition (EMT) in cancer stroma contribute to tumor progression and metastasis. However, no reports have investigated the CAF phenotype and its clinicopathological relevance in cutaneous malignant tumors, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). Here, we investigated the CAF phenotype in cutaneous malignant tumors based on their histology and immunohistochemical expression of CAF-related markers, including adipocyte enhancer-binding protein 1 (AEBP1), podoplanin, platelet derived growth factor receptor α (PDGFRα), PDGFRβ, fibroblast activating protein (FAP), CD10, S100A4, α-smooth muscle actin (α-SMA), and EMT-related markers (Zeb1, Slug and Twist)...
March 16, 2018: Human Pathology
https://www.readbyqxmd.com/read/29545370/pdgfr%C3%AE-translocates-to-the-nucleus-and-regulates-chromatin-remodeling-via-tata-element-modifying-factor-1
#11
Natalia Papadopoulos, Johan Lennartsson, Carl-Henrik Heldin
Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB-induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells...
March 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29544149/discovery-of-4-n-2-dimethylamino-ethyl-acrylamido-methyl-n-4-methyl-3-4-pyridin-3-yl-pyrimidin-2-yl-amino-phenyl-benzamide-chmfl-pdgfr-159-as-a-highly-selective-type-ii-pdgfr%C3%AE-kinase-inhibitor-for-pdgfr%C3%AE-driving-chronic-eosinophilic-leukemia
#12
Qiang Wang, Feiyang Liu, Shuang Qi, Ziping Qi, Xiao-E Yan, Beilei Wang, Aoli Wang, Wei Wang, Cheng Chen, Xiaochuan Liu, Zongru Jiang, Zhenquan Hu, Li Wang, Wenchao Wang, Tao Ren, Shanchun Zhang, Cai-Hong Yun, Qingsong Liu, Jing Liu
Through exploration of the non-highly conserved allosteric hydrophobic pocket generated by DFG-out shifting in the inactive conformation, we discovered a highly selective type II PDGFRα kinase inhibitor 15i (CHMFL-PDGFRα-159), which exhibited strong potency against purified PDGFRα (IC50 : 132 nM) but not structurally similar PDGFRβ, ABL, c-KIT and VEGFR2 kinases. In addition, it displayed a high selectivity profile (S score (10) = 0.02) at the concentration of 1 μM among 468 kinases/mutants in the KINOMEscan profiling...
March 12, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29543041/neuropilin-1and-platelet-derived-growth-factor-receptors-cooperatively-regulate-intermediate-filaments-and-mesenchymal-cell-migration-during-alveolar-septation
#13
Stephen E McGowan, Diann M McCoy
Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29534963/s1p-s1pr3-signaling-mediated-proliferation-of-pericytes-via-ras-perk-pathway-and-cay10444-had-beneficial-effects-on-spinal-cord-injury
#14
Hai-Bin Tang, Xiao-Jian Jiang, Chen Wang, Shi-Chang Liu
Pericytes have long been regarded merely to maintain structural and functional integrity of blood-brain barrier (BBB). Nevertheless, it has also been identified as a component of scar-forming stromal cells after spinal cord injury (SCI). In process of enlargement of spinal cavity after SCI, the number of pericytes increased and outnumbered astrocytes. However, the mechanism of proliferation of pericytes remains unclear. Sphingosine-1-phosphate (S1P) has been reported to play important roles in the formation of glia scar, but previous studies had paid more attention to the astrocytes...
March 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29518779/clinical-and-biomarker-evaluations-of-sunitinib-in-patients-with-grade-3-digestive-neuroendocrine-neoplasms
#15
Anna Pellat, Chantal Dreyer, Camille Couffignal, Thomas Walter, Catherine Lombard-Bohas, Patricia Niccoli, Jean François Seitz, Olivia Hentic, Thierry André, Romain Coriat, Sandrine Faivre, Magaly Zappa, Philippe Ruszniewski, Nicolas Pote, Anne Couvelard, Eric Raymond
BACKGROUND/AIMS: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. METHODS: Sunitinib was given at a dose of 37...
March 8, 2018: Neuroendocrinology
https://www.readbyqxmd.com/read/29513717/an-anti-pdgfr%C3%AE-aptamer-for-selective-delivery-of-small-therapeutic-peptide-to-cardiac-cells
#16
Alessandra Romanelli, Alessandra Affinito, Concetta Avitabile, Silvia Catuogno, Paola Ceriotti, Margherita Iaboni, Jessica Modica, Geroloma Condorelli, Daniele Catalucci
Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitations on their conjugation to small peptides and the functionality of the resulting aptamer-peptide chimera exist. Here, we generated a novel aptamer-peptide chimera through conjugation of the PDGFRβ-targeting Gint4...
2018: PloS One
https://www.readbyqxmd.com/read/29511648/exercise-training-regulates-angiogenic-gene-expression-in-white-adipose-tissue
#17
Hyuek Jong Lee
White adipose tissue (WAT) expansion is associated with angiogenesis. Although, activation of lipolysis by exercise induces adipocyte hypotrophy and reduction of fat mass, it is poorly understood whether exercise regulates angiogenesis by altering angiogenic gene expression in WAT. Therefore, the purpose of this study was to evaluate the effect of 6 weeks voluntary wheel running exercise on angiogenic gene expression in adipose tissues. Male C57BL/6J mice performed voluntary wheel running for 6 weeks. At 24 hr after the last exercise training, tibialis anterior (TA), soleus (Sol), epididymal WAT (eWAT), inguinal WAT (iWAT), and brown adipose tissue (BAT) were isolated and then the expressions of vascular endothelial growth factor A (VEGFA), angiopoietin1 (Ang1), Ang2, platelet-derived growth factor B (PDGF-B) and their corresponding receptors were analyzed by reverse transcription-polymerase chain reaction...
February 2018: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/29507818/lrp1-in-osteoblasts-controls-osteoclast-activity-and-protects-against-osteoporosis-by-limiting-pdgf-rankl-signaling
#18
Alexander Bartelt, Friederike Behler-Janbeck, F Timo Beil, Till Koehne, Brigitte Müller, Tobias Schmidt, Markus Heine, Laura Ochs, Tayfun Yilmaz, Martin Dietrich, Jan P Tuckermann, Michael Amling, Joachim Herz, Thorsten Schinke, Joerg Heeren, Andreas Niemeier
Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption...
2018: Bone Research
https://www.readbyqxmd.com/read/29499951/stat3-gene-silencing-by-aptamer-sirna-chimera-as-selective-therapeutic-for-glioblastoma
#19
Carla Lucia Esposito, Silvia Nuzzo, Silvia Catuogno, Simona Romano, Filomena de Nigris, Vittorio de Franciscis
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults, and despite advances in neuro-oncology, the prognosis for patients remains dismal. The signal transducer and activator of transcription-3 (STAT3) has been reported as a key regulator of the highly aggressive mesenchymal GBM subtype, and its direct silencing (by RNAi oligonucleotides) has revealed a great potential as an anti-cancer therapy. However, clinical use of oligonucleotide-based therapies is dependent on safer ways for tissue-specific targeting and increased membrane penetration...
March 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29497032/de-novo-adipocyte-differentiation-from-pdgfr%C3%AE-preadipocytes-protects-against-pathologic-visceral-adipose-expansion-in-obesity
#20
Mengle Shao, Lavanya Vishvanath, Napoleon C Busbuso, Chelsea Hepler, Bo Shan, Ankit X Sharma, Shiuhwei Chen, Xinxin Yu, Yu A An, Yi Zhu, William L Holland, Rana K Gupta
Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potential to recruit new adipocytes from Pdgfrβ+ preadipocytes determines visceral WAT health in obesity. We manipulate levels of Pparg, the master regulator of adipogenesis, in Pdgfrβ+ precursors of adult mice. Increasing the adipogenic capacity of Pdgfrβ+ precursors through Pparg overexpression results in healthy visceral WAT expansion in obesity and adiponectin-dependent improvements in glucose homeostasis...
March 1, 2018: Nature Communications
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