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https://www.readbyqxmd.com/read/28817816/exosomes-derived-from-human-bone-marrow-mesenchymal-stem-cells-promote-tumor-growth-through-hedgehog-signaling-pathway
#1
Jin Qi, Yali Zhou, Zuoyi Jiao, Xu Wang, Yang Zhao, Yangbin Li, Huijuan Chen, Luxi Yang, Hongwen Zhu, Yumin Li
BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28810570/research-on-the-function-and-related-mechanism-of-p27-gene-in-the-intervertebral-disc-degeneration-of-mice
#2
Xiao Liu, Deguo Wang, Zhengzheng Zhang, Fenghui Zhu, Aiming Yao, Jiwei Tian, Dengshun Miao
This study aims to investigate the function and related mechanism of P27 gene in intervertebral disc (IVD) degeneration of mice. X-ray, immunohistochemical staining, and alkaline phosphatase (ALP) histochemical staining were used to analyze the phenotypic difference of the intervertebral discs of 4-week-old mice with P27 gene knockout (P27(-/-)) and wild-type (WT) mice in the same brood. Protein in the intervertebral disc was extracted and western blot analysis was employed to detect the changes in the expression of related molecules in the Shh-signal pathways, including Shh, Patched, Smoothened and Gli2...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808827/distinctive-localization-and-mri-features-correlate-of-molecular-subgroups-in-adult-medulloblastoma
#3
Fu Zhao, Chunde Li, Qiangyi Zhou, Peiran Qu, Bo Wang, Xin Wang, Shun Zhang, Xingchao Wang, Chi Zhao, Jing Zhang, Lin Luo, Lin Ai, Lei Xu, Pinan Liu
Medulloblastoma (MB) is recognized as comprising four molecular subgroups with distinct transcriptional profiles, clinical features, and outcomes. Previous studies demonstrate that pediatric MBs present with subgroup-specific MRI manifestations. We hypothesized that combination of anatomical localization and conventional features based on MR imaging can predict these subgroups in adult MBs. MR Imaging manifestations of 125 adult patients with MB were analyzed retrospectively based on pre-operative MRI scans...
August 14, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28807898/hypothalamic-sonic-hedgehog-is-required-for-cell-specification-and-proliferation-of-lhx3-lhx4-pituitary-embryonic-precursors
#4
G Carreno, J Apps, E J Lodge, L Panousopoulos, S Haston, J M Gonzalez-Meljem, H Hahn, C L Andoniadou, J P Martinez-Barbera
Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28807896/fgf10-progenitors-give-rise-to-the-chick-hypothalamus-by-rostral-and-caudal-growth-and-differentiation
#5
Travis Fu, Matthew Towers, Marysia Placzek
Classical descriptions of the hypothalamus divide it into three rostro-caudal domains but little is known about their embryonic origins. To investigate this we performed targeted fate-mapping, molecular characterisation and cell cycle analyses in the embryonic chick. Presumptive hypothalamic cells derive from the rostral diencephalic ventral midline, lie above the prechordal mesendoderm and express Fgf10Fgf10(+) progenitors undergo anisotropic growth: those displaced rostrally differentiate into anterior cells, then those displaced caudally differentiate into mammillary cells...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28799057/expression-patterns-of-key-sonic-hedgehog-signaling-pathway-components-in-the-developing-and-adult-mouse-midbrain-and-in-the-mn9d-cell-line
#6
Melanie Feuerstein, Enaam Chleilat, Shokoufeh Khakipoor, Konstantinos Michailidis, Christian Ophoven, Eleni Roussa
The temporal dynamic expression of Sonic Hedgehog (SHH) and signaling during early midbrain dopaminergic (mDA) neuron development is one of the key players in establishing mDA progenitor diversity. However, whether SHH signaling is also required during later developmental stages and in mature mDA neurons is less understood. We study the expression of SHH receptors Ptch1 and Gas1 (growth arrest-specific 1) and of the transcription factors Gli1, Gli2 and Gli3 in mouse midbrain during embryonic development [embryonic day (E) 12...
August 11, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28798218/imaging-biomarkers-for-adult-medulloblastomas-genetic-entities-may-be-identified-by-their-mr-imaging-radiophenotype
#7
V C Keil, M Warmuth-Metz, C Reh, S J Enkirch, C Reinert, D Beier, D T W Jones, T Pietsch, H H Schild, E Hattingen, P Hau
BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists...
August 10, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28797840/nerves-h2o2-and-shh-three-players-in-the-game-of-regeneration
#8
REVIEW
Francesca Meda, Christine Rampon, Edmond Dupont, Carole Gauron, Aurélien Mourton, Isabelle Queguiner, Marion Thauvin, Michel Volovitch, Alain Joliot, Sophie Vriz
The tight control of reactive oxygen species (ROS) levels is required during regeneration. H2O2 in particular assumes clear signalling functions at different steps in this process. Injured nerves induce high levels of H2O2 through the activation of the Hedgehog (Shh) pathway, providing an environment that promotes cell plasticity, progenitor recruitment and blastema formation. In turn, high H2O2 levels contribute to growing axon attraction. Once re-innervation is completed, nerves subsequently downregulate H2O2 levels to their original state...
August 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28797033/a-shh-foxf1-bmp4-signaling-axis-regulating-growth-and-differentiation-of-epithelial-and-mesenchymal-tissues-in-ureter-development
#9
Tobias Bohnenpoll, Anna B Wittern, Tamrat M Mamo, Anna-Carina Weiss, Carsten Rudat, Marc-Jens Kleppa, Karin Schuster-Gossler, Irina Wojahn, Timo H-W Lüdtke, Mark-Oliver Trowe, Andreas Kispert
The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH) family of secreted proteins, Sonic hedgehog (SHH) as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO) to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development...
August 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28793263/the-conserved-sonic-hedgehog-limb-enhancer-consists-of-discrete-functional-elements-that-regulate-precise-spatial-expression
#10
Laura A Lettice, Paul Devenney, Carlo De Angelis, Robert E Hill
Expression of sonic hedgehog (Shh) in the limb bud is regulated by an enhancer called the zone of polarizing activity regulatory sequence (ZRS), which, in evolution, belongs to an ancient group of highly conserved cis regulators found in all classes of vertebrates. Here, we examined the endogenous ZRS in mice, using genome editing to establish the relationship between enhancer composition and embryonic phenotype. We show that enhancer activity is a consolidation of distinct activity domains. Spatial restriction of Shh expression is mediated by a discrete repressor module, whereas levels of gene expression are controlled by large overlapping domains containing varying numbers of HOXD binding sites...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28793255/%C3%AE-e-catenin-is-a-positive-regulator-of-pancreatic-islet-cell-lineage-differentiation
#11
Antonio J Jimenez-Caliani, Rudolf Pillich, Wendy Yang, Giuseppe R Diaferia, Paolo Meda, Laura Crisa, Vincenzo Cirulli
The development and function of epithelia depend on the establishment and maintenance of cell-cell adhesion and intercellular junctions, which operate as mechanosensor hubs for the transduction of biochemical signals regulating cell proliferation, differentiation, survival, and regeneration. Here, we show that αE-catenin, a key component of adherens junctions, functions as a positive regulator of pancreatic islet cell lineage differentiation by repressing the sonic hedgehog pathway (SHH). Thus, deletion of αE-catenin in multipotent pancreatic progenitors resulted in (1) loss of adherens junctions, (2) constitutive activation of SHH, (3) decrease in islet cell lineage differentiation, and (4) accumulation of immature Sox9(+) progenitors...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28781964/loss-of-suppressor-of-fused-in-mid-corticogenesis-leads-to-the-expansion-of-intermediate-progenitors
#12
Odessa R Yabut, Hui Xuan Ng, Gloria Fernandez, Keejung Yoon, Jeremy Kuhn, Samuel J Pleasure
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene...
December 2016: Journal of Developmental Biology
https://www.readbyqxmd.com/read/28778067/exome-sequencing-analysis-of-murine-medulloblastoma-models-identifies-wdr11-as-a-potential-tumor-suppressor-in-group-3-tumors
#13
Lei Wei, Brian L Murphy, Gang Wu, Matthew Parker, John Easton, Richard J Gilbertson, Jinghui Zhang, Martine F Roussel
Mouse models of human cancers are widely used in cancer research, yet questions frequently arise regarding their faithfulness in recapitulating their human counterparts. To compare the somatic mutations of murine models with human medulloblastoma (MB), we performed whole-exome sequencing on 12 tumors representing three distinct medulloblastoma subgroups: Wnt, Sonic Hedgehog (Shh) and Group 3 (G3). In total, 64 somatic mutations were identified and validated, including 40 predicted to cause amino acid changes...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28771384/vax1-plays-an-indirect-role-in-the-etiology-of-murine-cleft-palate
#14
F Geoghegan, G M Xavier, A A Birjandi, M Seppala, M T Cobourne
Cleft lip with or without palate (CLP) and isolated cleft palate (CP) are common human developmental malformations with a complex etiology that reflects a failure of normal facial development. VAX1 encodes a homeobox-containing transcription factor identified as a candidate gene for CLP in human populations, with targeted deletion in mice associated with multiple anomalies, including disruption of the visual apparatus and basal forebrain, lobar holoprosencephaly, and CP. We have investigated Vax1 function during murine palatogenesis but found no evidence for a direct role in this process...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28765042/mir-342-3p-elevates-osteogenic-differentiation-of-umbilical-cord-mesenchymal-stem-cells-via-inhibiting-sufu-in%C3%A2-vitro
#15
Mengqi Huang, Ying Qing, Qi Shi, Yingguang Cao, Ke Song
Human umbilical mesenchymal stem cells (UCMSCs) have been wildly used in tissue engineering field as a promising source because of their unlimited and noninvasive origin. To selectively induce osteogenic differentiation of UCMSCs, it's imperative to understand the regulatory molecular mechanism underlying the process of how these cells switch into osteogenic lineage path. We previously showed enhanced sonic hedgehog (Shh) signaling pathway upon osteogenic induction in mesenchymal stem cells. In this study, miRNA-seq analysis revealed substantial Shh-dependent expression of distinct miRNAs, including miR-342-3p, during ostogenesis...
July 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28759213/design-and-evolution-of-a-macrocyclic-peptide-inhibitor-of-the-sonic-hedgehog-patched-interaction
#16
Andrew E Owens, Ivan de Paola, William A Hansen, Yi-Wen Liu, Sagar D Khare, Rudi Fasan
The Hedgehog (Hh) signaling pathway plays a central role during embryonic development and its aber-rant activation has been implicated in the development and progression of several human cancers. Ma-jor efforts toward the identification of chemical modulators of the Hedgehog pathway has yielded sev-eral antagonists of the GPCR-like Smoothened receptor. In contrast, potent inhibitors of the Sonic Hedgehog/Patched interaction, the most upstream event in ligand-induced activation of this signaling pathway, have been elusive...
July 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28757413/restoration-of-mir-30a-expression-inhibits-growth-tumorigenicity-of-medulloblastoma-cells-accompanied-by-autophagy-inhibition
#17
Satishkumar Vishram Singh, Aditi Nigam Dakhole, Akash Deogharkar, Sadaf Kazi, Rohan Kshirsagar, Atul Goel, Aliasgar Moiyadi, Rakesh Jalali, Epari Sridhar, Tejpal Gupta, Prakash Shetty, Nikhil Gadewal, Neelam Vishwanath Shirsat
Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients have metastasis at diagnosis and respond poorly to treatment. Those that survive, suffer long term neurocognitive, endocrine and developmental defects due to the cytotoxic treatment to developing child brain. It is therefore necessary to develop targeted treatment strategies based on underlying biology for effective treatment of medulloblastoma with minimal side effects. Medulloblastomas are believed to be the result of deregulated nervous system development as evident from the role of WNT and SHH developmental signaling pathways in pathogenesis of medulloblastomas...
July 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28747625/the-regulation-of-hh-gli1-signaling-cascade-involves-gsk3%C3%AE-mediated-mechanism-in-estrogen-derived-endometrial-hyperplasia
#18
Jyoti Bala Kaushal, Pushplata Sankhwar, Suparna Kumari, Pooja Popli, Vinay Shukla, Mohd Kamil Hussain, Kanchan Hajela, Anila Dwivedi
The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3β was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3β whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743797/sonic-hedgehog-from-both-nerves-and-epithelium-is-a-key-trophic-factor-for-taste-bud-maintenance
#19
David Castillo-Azofeifa, Justin T Losacco, Ernesto Salcedo, Erin J Golden, Thomas E Finger, Linda A Barlow
The integrity of taste buds is intimately dependent on an intact gustatory innervation, yet the molecular nature of this dependency is unknown. Here we show differentiation of new taste bud cells, but not progenitor proliferation, is interrupted in mice treated with a Hedgehog (Hh) pathway inhibitor (HPI), and that gustatory nerves are a source of Shh for taste bud renewal. Additionally, epithelial taste precursor cells express Shh transiently, and are a local supply of Hh ligand supporting taste cell renewal...
July 25, 2017: Development
https://www.readbyqxmd.com/read/28739739/transcriptional-profiling-of-sonic-hedgehog-in-a-prospective-cohort-of-breast-cancer-in-a-pakistani-population
#20
Syeda Kiran Riaz, Lin Ye, Namood E Sahar, Durkhshan Aman, Javeria Qadir, Jahangir Sarwar Khan, Muhammad Saeed, Wen G Jiang, Muhammad Faraz Arshad Malik
BACKGROUND/AIM: Constitutive activation of Sonic hedgehog (SHH) has been observed in different types of cancers. In the present study, expressional profiling of SHH in a breast cancer cohort (n=150) of a Pakistani population and its association with different molecular subtypes have been explored. MATERIALS AND METHODS: qRT-PCR and IHC were performed for expression analysis of SHH and its association with ER, PR, HER2 and Ki-67 were also statistically analyzed. RESULTS: A significant over-expression of SHH was observed in tumor tissues in comparison to their respective controls (p<0...
August 2017: Anticancer Research
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