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Hedgehog signalling pathway

Heping Huang, Shangfeng Fu, Dewu Liu
BACKGROUND Hedgehog (Hh) signaling pathway-related genes have important roles in several physiological and disease processes that involve cell proliferation. Long non-coding region RNAs (lncRNAs) have a regulatory role on gene expression. Keloid is characterized by excessive proliferation of scar tissue following trauma. The aims of this study were to evaluate the Hh signaling pathway in keloid skin tissues and its downstream gene expression and lncRNAs, compared with normal skin. MATERIAL AND METHODS Four pairs of keloids and adjacent normal skin epidermis underwent total RNA extraction...
December 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Shital Sarah Ahaley
In Hedgehog (Hh) signalling, Hh ligand concentration gradient is effectively translated into a spatially distinct transcriptional program to give precisely controlled context dependent developmental outcomes. In the absence of Hh, the receptor Patched (Ptc) inhibits the signal transducer Smoothened (Smo) by maintaining low phosphatidylinositol 4-phosphate (PI(4)P) levels. Binding of Hh to its receptor Ptc promotes PI(4)P production, which in turn activates Smo. Using wingdiscs of Drosophila melanogaster , this study shows that Synaptojanin (Synj), a dual phosphatase, modulates PI(4)P levels and affects Smo activation, and thereby functions as an additional regulatory step in the Hh pathway...
December 2018: Journal of Biosciences
Cecile Giordano, Laurent Ruel, Candice Poux, Pascal Therond
Hedgehog (Hh) is a conserved morphogen that controls cell differentiation and tissue patterning in metazoans. In Drosophila , the Hh signal is transduced from the G protein-coupled receptor Smoothened (Smo) to the cytoplasmic Hh signaling complex (HSC). How activated Smo is translated into a graded activation of the downstream pathway is still not well understood. In this study, we show that the last amino acids of the cytoplasmic tail of Smo, in combination with G protein-coupled receptor kinase 2 (Gprk2), bind to the regulatory domain of Fused (Fu) and highly activate its kinase activity...
December 12, 2018: Development
Weichao Zhao, Nan Hu, Dexin Ding, Dingxin Long, Sheng Li, Guangyue Li, Hui Zhang
In this paper, the developmental toxicity and apoptosis in zebrafish (Danio rerio) embryos induced by 0.01, 0.05, and 0.10-Gy γ-ray irradiation were investigated and verified by single cell gel electrophoresis, acridine orange staining, flow cytometry, transmission electron microscopy, digital gene expression sequencing, and Western blot analysis. DNA damage, deformity rates, and apoptosis of zebrafish embryos were found to increase significantly with the increase of irradiation dose, and survival and hatching rates significantly decreased when the irradiation dose exceeds 0...
December 12, 2018: Environmental Science and Pollution Research International
Danli Cai, Jianshun Yu, Jing Qiu, Beihui He, Zhiyun Chen, Maoxiang Yan, Qingsheng Liu
OBJECTIVE: To explore the changes of Sonic Hedgehog (Shh) signaling pathway in the stomach mucosa during the formation of gastric precancerous lesions. METHODS: A total of 72 suckling rats in half genders were randomly and equally divided into the normal group and model group. The rats in the model group were administered with 0.1 ml 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at the dosage of 800 mg/L for 10 days, whereas the rats in the normal group were similarly administered with normal saline...
December 7, 2018: Journal of Cellular Physiology
Zahra Asadzadeh, Behzad Mansoori, Ali Mohammadi, Marjan Aghajani, Khalil Haji-Asgarzadeh, Elham Safarzadeh, Ahad Mokhtarzadeh, Pascal H G Duijf, Behzad Baradaran
Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self-renewal capacity, low proliferation rate, and tumor-initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. The molecular mechanisms underlying CSC biology are now beginning to be understood. In this context, microRNAs (miRNAs) occupy a prominent place...
December 7, 2018: Journal of Cellular Physiology
Li-Hua Guo, Yu Cao, Run-Tao Zhuang, Yan Han, Jun Li
The present study aimed to investigate the effects of astragaloside IV on osteoblast‑like cell proliferation and migration, in addition to the underlying signaling pathway. In order to observe the effect on proliferation, a Cell Counting Kit‑8 assay and flow cytometry were used. To detect cell migration ability, cell scratch and Transwell cell migration assays were performed. The RNA and protein expression levels of hedgehog signaling molecules, including Sonic hedgehog (SHH) and GLI family zinc finger 1 (GLI1), were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses...
December 3, 2018: International Journal of Molecular Medicine
Susmita Mondal, Kaushik Bhattacharya, Chitra Mandal
The emergence and maintenance of cancer stem-like cells (CSCs) are usually governed by tumor niche. Tumor niche always provides metabolic challenges to cancer cells and CSCs mostly because of tissue hypoxia. However, the role of micro-environmental nutritional stress (NS) in dedifferentiation of cancer cells is poorly defined. Here, we developed a stochastic model of CSCs by gradual nutritional deprivation in glioblastoma multiforme (GBM) cells used as a model system. Nutritional deprivation induced enhanced expression of glioblastoma stem-like cells (GSCs)-specific biomarkers with higher invasive and angiogenic properties...
2018: Cell Death Discovery
Emily Bowie, Ryan Norris, Kathryn V Anderson, Sarah C Goetz
Spinocerebellar ataxia type 11 (SCA11) is a rare, dominantly inherited human ataxia characterized by atrophy of Purkinje neurons in the cerebellum. SCA11 is caused by mutations in the gene encoding the Serine/Threonine kinase Tau tubulin kinase 2 (TTBK2) that result in premature truncations of the protein. We previously showed that TTBK2 is a key regulator of the assembly of primary cilia in vivo. However, the mechanisms by which the SCA11-associated mutations disrupt TTBK2 function, and whether they interfere with ciliogenesis were unknown...
December 10, 2018: PLoS Genetics
Ramesh Butti, Vinoth Prasanna Gunasekaran, Totakura V S Kumar, Pinaki Banerjee, Gopal C Kundu
Breast cancer remains to be a dreadful disease even with several advancements in radiation and chemotherapies, owing to the drug resistance and tumor relapse caused by breast cancer stem cells. Cancer stem cells are minute population of cells of solid tumors which show self-renewal and differentiation properties as well as tumorigenic potential. Several signaling pathways including Notch, Hippo, Wnt and Hedgehog and tumor-stroma exchanges play a critical role in the self-renewal and differentiation of cancer stem cells in breast cancer...
December 5, 2018: International Journal of Biochemistry & Cell Biology
Kelly A Teske, Radha Charan Dash, Shana R Morel, Lianne Q Chau, Robert J Wechsler-Reya, M Kyle Hadden
Inhibition of the hedgehog (Hh) signaling pathway has been validated as a therapeutic strategy to treat basal cell carcinoma and holds potential for several other forms of human cancer. Itraconazole and posaconazole are clinically useful triazole anti-fungals that are being repurposed as anti-cancer agents based on their ability to inhibit the Hh pathway. We have previously demonstrated that removal of the triazole from itraconazole does not affect its ability to inhibit the Hh pathway while abolishing its primary side effect, potent inhibition of Cyp3A4...
November 23, 2018: European Journal of Medicinal Chemistry
Jennifer Zur Bruegge, Marc Bohmer, Elisabeth Hahn, Claudia Steiner, Ralf Einspanier, Soroush Sharbati
The hedgehog signaling pathway is a crucial regulator of the postnatal intestinal development. Regulation of hedgehog expression itself is poorly understood. MicroRNAs were demonstrated to control differentiation and proliferation in postnatal intestinal development. This study identifies members of the miR-15 family to regulate the expression of key hedgehog factors employing in silico and in vitro experiments. Physiological relevance is demonstrated by incorporation of in vivo expression data from the ileum and colon from 7 to 56 days old piglets...
December 7, 2018: Biochemical and Biophysical Research Communications
William R Swindell, Krzysztof Bojanowski, Mark S Kindy, Raymond M W Chau, Dorothy Ko
Background: Amyotrophic lateral sclerosis (ALS) is currently an incurable disease without highly effective pharmacological treatments. The peptide drug GM604 (GM6 or Alirinetide) was developed as a candidate ALS therapy, which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic profile. GM6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways, but mechanisms of action are not fully understood. Methods: This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment (6, 24 and 48 h)...
2018: Translational Neurodegeneration
Nabila Bahrami, Sarah J Childs
The zebrafish is an outstanding model for studying vascular biology in vivo. Pericytes and vascular smooth muscle cells can be imaged as they associate with vessels and provide stability and integrity to the vasculature. In zebrafish, pericytes associate with the cerebral and trunk vasculature on the second day of development, as assayed by pdgfrβ and notch3 markers. In the head, cerebral pericytes are neural crest derived, except for the pericytes of the hindbrain vasculature, which are mesoderm derived. Similar to the hindbrain, pericytes on the trunk vasculature are also mesoderm derived...
2018: Advances in Experimental Medicine and Biology
Genovefa Polychronidou, Vassiliki Kotoula, Kyriaki Manousou, Ioannis Kostopoulos, Georgia Karayannopoulou, Eleni Vrettou, Mattheos Bobos, Georgia Raptou, Ioannis Efstratiou, Dimitrios Dionysopoulos, Kyriakos Chatzopoulos, Sotirios Lakis, Sofia Chrisafi, Dimitrios Tsolakidis, Alexios Papanikolaou, Nikolaos Dombros, George Fountzilas
The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of endometrial cancer, in association with clinical outcome and standard clinicopathological characteristics. A total of 204 patients with histological diagnosis of endometrial cancer treated from 2004 to 2013 were included...
2018: PloS One
Alexander Herholt, Ben Brankatschk, Nirmal Kannaiyan, Sergi Papiol, Sven P Wichert, Michael C Wehr, Moritz J Rossner
Neuronal signal transduction shapes brain function and malfunction may cause mental disorders. Despite the existence of functional genomics screens for proliferation and toxicity, neuronal signalling has been difficult to address so far. To overcome this limitation, we developed a pooled screening assay which combines barcoded activity reporters with pooled genetic perturbation in a dual-expression adeno-associated virus (AAV) library. With this approach, termed pathScreener, we comprehensively dissect signalling pathways in postmitotic neurons...
December 4, 2018: Scientific Reports
Anindita Tripathy, Sudhir Thakurela, Manoj Kumar Sahu, Kanishka Uthanasingh, Manas Behera, Amrendra Kumar Ajay, Ratna Kumari
BACKGROUND: Hepatocellular carcinoma (HCC) is leading cause of cancer-related mortality and is categorized among the most common malignancies around the world. It is a heterogeneous tumor, which shows significant degree of histopathological heterogeneity. Despite the apparent histopathological diversity there has been very little distinct correlation between histopathological features and molecular aberrations particularly when it comes to the expression level of Wnt and Hh pathway molecules...
2018: PloS One
Artem Kim, Clara Savary, Christèle Dubourg, Wilfrid Carré, Charlotte Mouden, Houda Hamdi-Rozé, Hélène Guyodo, Jerome Le Douce, Laurent Pasquier, Elisabeth Flori, Marie Gonzales, Claire Bénéteau, Odile Boute, Tania Attié-Bitach, Joelle Roume, Louise Goujon, Linda Akloul, Sylvie Odent, Erwan Watrin, Valérie Dupé, Marie de Tayrac, Véronique David
Holoprosencephaly is a pathology of forebrain development characterized by high phenotypic heterogeneity. The disease presents with various clinical manifestations at the cerebral or facial levels. Several genes have been implicated in holoprosencephaly but its genetic basis remains unclear: different transmission patterns have been described including autosomal dominant, recessive and digenic inheritance. Conventional molecular testing approaches result in a very low diagnostic yield and most cases remain unsolved...
November 30, 2018: Brain: a Journal of Neurology
Mubeena Mariyath P M, Mehdi H Shahi, Mohd Tayyab, Shirin Farheen, Nabeela Khanam, Sartaj Tabassum, Asif Ali
BACKGROUND: Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. OBJECTIVES: This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. METHODS: Total 18 male Wistar rats were randomly divided into two groups, control and test groups...
December 1, 2018: Journal of Biochemical and Molecular Toxicology
Amar N Mirza, Siegen A McKellar, Nicole M Urman, Alexander S Brown, Tyler Hollmig, Sumaira Z Aasi, Anthony E Oro
Understanding transcription factor navigation through the nucleus remains critical for developing targeted therapeutics. The GLI1 transcription factor must maintain maximal Hedgehog pathway output in basal cell carcinomas (BCCs), and we have previously shown that resistant BCCs increase GLI1 deacetylation through atypical protein kinase Cι/λ (aPKC) and HDAC1. Here we identify a lamina-associated polypeptide 2 (LAP2) isoform-dependent nuclear chaperoning system that regulates GLI1 movement between the nuclear lamina and nucleoplasm to achieve maximal activation...
November 27, 2018: Cell
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