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https://www.readbyqxmd.com/read/29054607/repigmentation-of-human-vitiligo-skin-by-nbuvb-is-controlled-by-transcription-of-gli1-and-activation-of-%C3%AE-catenin-pathway-in-the-hair-follicle-bulge-stem-cells
#1
Nathaniel B Goldstein, Maranke I Koster, Kenneth L Jones, Bifeng Gao, Laura G Hoaglin, Steven E Robinson, Michael J Wright, Smaranda I Birlea, Abigail Luman, Karoline A Lambert, Yiqun G Shellman, Mayumi Fujita, William A Robinson, Dennis R Roop, David A Norris, Stanca A Birlea
Vitiligo repigmentation is a complex process in which the melanocyte-depleted interfollicular epidermis (IE) is repopulated by melanocyte precursors from hair follicle (HF) bulge that proliferate, migrate, and differentiate into mature melanocytes on their way to the epidermis. The strongest stimulus for vitiligo repigmentation is narrow band UVB (NBUVB), but how the HF melanocyte precursors are activated by UV light has not been extensively studied. To better understand this process, we developed an application that combined laser capture microdissection and subsequent whole transcriptome RNA sequencing of HF bulge melanocyte precursors, and compared their gene signature to that of regenerated mature epidermal melanocytes from the NBUVB-treated vitiligo skin...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29045809/postnatal-sonic-hedgehog-shh-responsive-cells-give-rise-to-oligodendrocyte-lineage-cells-during-myelination-and-in-adulthood-contribute-to-remyelination
#2
Maria A Sanchez, Regina C Armstrong
Sonic hedgehog (Shh) regulates a wave of oligodendrocyte production for extensive myelination during postnatal development. During this postnatal period of oligodendrogenesis, we fate-labeled cells exhibiting active Shh signaling to examine their contribution to the regenerative response during remyelination. Bitransgenic mouse lines were generated for induced genetic fate-labeling of cells actively transcribing Shh or Gli1. Gli1 transcription is an effective readout for canonical Shh signaling. Shh(CreERT2) mice and Gli1(CreERT2) mice were crossed to either R26(tdTomato) mice to label cells with red fluorescence, or, R26(IAP) mice to label membranes with alkaline phosphatase...
October 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29039491/non-canonical-hedgehog-signaling-activation-in-ovarian-borderline-tumors-and-ovarian-carcinomas
#3
Petar Ozretić, Diana Trnski, Vesna Musani, Ivana Maurac, Držislav Kalafatić, Slavko Orešković, Sonja Levanat, Maja Sabol
Hedgehog signaling pathway has been implicated in the pathology of ovarian cancer, and Survivin (BIRC5) has been suggested as a novel target of this pathway. Herein we investigated the role of Hedgehog signaling pathway and Survivin in ovarian carcinoma and borderline tumor samples. We aimed to determine possible ways of pathway modulation on primary ovarian cancer cells and an established cell line. RNA was extracted from fresh tumors and control tissues and gene expression was examined using qRT-PCR. Pathway activity in cell lines was examined after treatment with cyclopamine, SHH protein, GANT-61 or lithium chloride using qRT-PCR, western blot and confocal microscopy...
October 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28994542/-mechanism-of-ezhu-containing-serum-in-inhibiting-expression-of-shh-and-gli1-in-hepatic-stellate-cells
#4
Li-Li Feng, Wen-Fu Cao
To explore the mechanism of Ezhu-containing serum in inhibiting the expression of sonic hedgehog(Shh) and glioma-associated oncogene homolog-1(Gli1) in hepatic stellate cells(HSCs) induced by leptin. Twenty sprague-dawley (SD) rats were randomly divided into 2 groups (n=10), and given Ezhu-decoction and physiological saline by gavage for 10 days to prepare drug-containing serums. The HSCs during the exponential growth phase were divided into 7 groups: blank control group, model group, hedgehog pathway inhibitor(cyclopamine) group, Ezhu group, Ezhu and cyclopamine group, hedgehog pathway agonost(pumorphamine) group, Ezhu and purmorphamine group...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28986380/astrocytes-promote-medulloblastoma-progression-through-hedgehog-secretion
#5
Yongqiang Liu, Larra W Yuelling, Yuan Wang, Fang Du, Renata E Gordon, Jenny O'Brien, Jessica M Y Ng, Shannon Robins, Eric H Lee, Hailong Liu, Tom Curran, Zeng-Jie Yang
Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. While astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secreted the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1)...
October 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28981158/low-intensity-pulsed-ultrasound-stimulation-promotes-osteoblast-differentiation-through-hedgehog-signaling
#6
Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Pang Pai, Yuu Horikiri, Nobuyuki Yamanaka, Masaharu Takigawa, Akira Sasaki
Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group...
October 5, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28978016/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#7
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976809/lepr-cells-dispute-hegemony-with-gli1-cells-in-bone-marrow-fibrosis
#8
Isadora F G Sena, Isabella T Borges, Luiza Lousado, Patrick O Azevedo, Julia P Andreotti, Viviani M Almeida, Ana E Paiva, Gabryella S P Santos, Daniel A P Guerra, Pedro H D M Prazeres, Luanny Souto, Akiva Mintz, Alexander Birbrair
Bone marrow fibrosis is a reactive process, and a central pathological feature of primary myelofibrosis. Revealing the origin of fibroblastic cells in the bone marrow is crucial, as these cells are considered an ideal, and essential target for anti-fibrotic therapy. In 2 recent studies, Decker et al. (2017) and Schneider et al. (2017), by using state-of-the-art techniques including in vivo lineage-tracing, provide evidence that leptin receptor (LepR)-expressing and Gli1-expressing cells are responsible for fibrotic tissue deposition in the bone marrow...
October 4, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28973407/gli1-inactivation-is-associated-with-developmental-phenotypes-overlapping-with-ellis-van-creveld-syndrome
#9
Adrian Palencia-Campos, Asmat Ullah, Julian Nevado, Ruken Yildirim, Edip Unal, Maria Ciorraga, Pilar Barruz, Lucia Chico, Francesca Piceci-Sparascio, Valentina Guida, Alessandro De Luca, Hülya Kayserili, Irfan Ullah, Margit Burmeister, Pablo Lapunzina, Wasim Ahmad, Aixa Morales, Victor L Ruiz-Perez
GLI1, GLI2 and GLI3 form a family of transcription factors which regulate development by mediating the action of Hedgehog (Hh) morphogens. Accordingly, inactivating variants in GLI2 and GLI3 are found in several developmental disorders. In contrast, loss-of-function mutations in GLI1 have remained elusive, maintaining enigmatic the role of this gene in the human embryo. We describe eight patients from three independent families having biallelic truncating variants in GLI1 and developmental defects overlapping with Ellis-van Creveld syndrome (EvC), a disease caused by diminished Hh signalling...
August 26, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28969581/molecular-modelling-of-berberine-derivatives-as-inhibitors-of-human-smoothened-receptor-and-hedgehog-signalling-pathway-using-a-newly-developed-algorithm-on-anti-cancer-drugs
#10
Parham Jabbarzadeh Kaboli, Mohammad Bazrafkan, Patimah Ismail, King-Hwa Ling
BACKGROUND: Protoberberine isoquinoline alkaloids are found in many plant species. They consist of a diverse class of secondary metabolites with many pharmacologically active members, such as different derivatives of berberine already patented. In the development of approximately 20-25% of all cancers, altered hedgehog (Hh) signalling is involved where the smoothened (Smo) transmembrane receptor triggers Hh signalling pathway towards Gli1 gene expression. OBJECTIVE: The current study aimed to model and verify the anti-Smo activity of berberine and its derivatives using a novel automated script...
September 29, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28965964/gli1-is-a-potential-cancer-stem-cell-marker-and-predicts-poor-prognosis-in-ductal-breast-carcinoma
#11
Weidong Ni, Zhaoting Yang, Wenbo Qi, Chunai Cui, Yan Cui, Yanhua Xuan
Glioma-associated oncogene homolog 1 (Gli1) maintains the cancer stem cell-like characteristics in various tumors. However, its expression in cancer stem cells (CSC) in ductal breast carcinoma has not been well studied. We aimed to characterize Gli1 as a potential CSC marker and investigate its clinical significance in ductal breast carcinoma. Immunohistochemical staining was used to study the relationship of Gli1 to clinicopathologic features, cell cycle regulation-related genes, and CSC markers. Gli1 was expressed to a greater extent in ductal breast carcinoma than in normal breast tissues (P=...
September 28, 2017: Human Pathology
https://www.readbyqxmd.com/read/28965853/pharmacological-targeting-of-gli1-inhibits-proliferation-tumor-emboli-formation-and-in%C3%A2-vivo-tumor-growth-of-inflammatory-breast-cancer-cells
#12
Helen O Oladapo, Michael Tarpley, Scott J Sauer, Kezia A Addo, Shalonda M Ingram, Dillon Strepay, Ben K Ehe, Lhoucine Chdid, Michael Trinkler, Jose R Roques, David B Darr, Jodie M Fleming, Gayathri R Devi, Kevin P Williams
Activation of the Hedgehog (Hh) pathway effector GLI1 is linked to tumorigenesis and invasiveness in a number of cancers, with targeting of GLI1 by small molecule antagonists shown to be effective. We profiled a collection of GLI antagonists possessing distinct mechanisms of action for efficacy in phenotypic models of inflammatory and non-inflammatory breast cancer (IBC and non-IBC) that we showed expressed varying levels of Hh pathway mediators. Compounds GANT61, HPI-1, and JK184 decreased cell proliferation, inhibited GLI1 mRNA expression and decreased the number of colonies formed in TN-IBC (SUM149) and TNBC (MDA-MB-231 and SUM159) cell lines...
September 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28954202/ciliopathy-protein-tmem107-plays-multiple-roles-in-craniofacial-development
#13
P Cela, M Hampl, N A Shylo, K J Christopher, M Kavkova, M Landova, T Zikmund, S D Weatherbee, J Kaiser, M Buchtova
A broad spectrum of human diseases called ciliopathies is caused by defective primary cilia morphology or signal transduction. The primary cilium is a solitary organelle that responds to mechanical and chemical stimuli from extracellular and intracellular environments. Transmembrane protein 107 (TMEM107) is localized in the primary cilium and is enriched at the transition zone where it acts to regulate protein content of the cilium. Mutations in TMEM107 were previously connected with oral-facial-digital syndrome, Meckel-Gruber syndrome, and Joubert syndrome exhibiting a range of ciliopathic defects...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28951519/degalactotigonin-a-natural-compound-from-solanum-nigrum-l-inhibits-growth-and-metastasis-of-osteosarcoma-through-gsk3%C3%AE-inactivation-mediated-repression-of-the-hedgehog-gli1-pathway
#14
Zhiqiang Zhao, Qiang Jia, Man-Si Wu, Xianbiao Xie, Yongqian Wang, Guohui Song, Chang-Ye Zou, Qinglian Tang, Jinchang Lu, Gang Huang, Jin Wang, De-Chen Lin, H Phillip Koeffler, Jun-Qiang Yin, Jingnan Shen
PURPOSE: Agents extracted from natural sources with anti-tumor property have attracted considerable attention from researchers and clinicians because of their safety, efficacy, and immediate availability. Degalactotigonin (DGT), extracted from Solanum nigrum L., has anticancer properties without serious side effects. Here, we explored whether DGT can inhibit the growth and metastasis of osteosarcoma. EXPERIMENTAL DESIGN: MTT, colony formation, and apoptosis assays were performed to analyze the effects of DGT on osteosarcoma cell viability in vitro...
September 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28929469/chondrocyte-expansion-is-associated-with-loss-of-primary-cilia-and-disrupted-hedgehog-signalling
#15
C L Thompson, J C Plant, A K Wann, C L Bishop, P Novak, H M Mitchison, P L Beales, J P Chapple, M M Knight
Tissue engineering-based therapies targeting cartilage diseases, such as osteoarthritis, require in vitro expansion of articular chondrocytes. A major obstacle for these therapies is the dedifferentiation and loss of phenotype accompanying chondrocyte expansion. Recent studies suggest that manipulation of hedgehog signalling may be used to promote chondrocyte re-differentiation. Hedgehog signalling requires the primary cilium, a microtubule-based signalling compartment, the integrity of which is linked to the cytoskeleton...
September 20, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28905994/microrna-324-5p-regulates-stemness-pathogenesis-and-sensitivity-to-bortezomib-in-multiple-myeloma-cells-by-targeting-hedgehog-signaling
#16
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of Hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28899410/nucleolar-and-spindle-associated-protein-1-promotes-the-aggressiveness-of-astrocytoma-by-activating-the-hedgehog-signaling-pathway
#17
Xianqiu Wu, Benke Xu, Chao Yang, Wentao Wang, Dequan Zhong, Zhan Zhao, Longshuang He, Yuanjun Hu, Lili Jiang, Jun Li, Libing Song, Wei Zhang
BACKGROUND: The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. METHODS: The expression of NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were analyzed by immunochemistry to demonstrate the correlation between the NUSAP1 expression and clinicopathological characteristics...
September 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28894158/biophysical-characterisation-of-the-novel-zinc-binding-property-in-suppressor-of-fused
#18
Amira Jabrani, Staëlle Makamte, Emilie Moreau, Yasmine Gharbi, Anne Plessis, Lucia Bruzzone, Matthieu Sanial, Valérie Biou
Suppressor of Fused (SUFU) is a highly conserved protein that acts as a negative regulator of the Hedgehog (HH) signalling pathway, a major determinant of cell differentiation and proliferation. Therefore, SUFU deletion in mammals has devastating effects on embryo development. SUFU is part of a multi-protein cytoplasmic signal-transducing complex. Its partners include the Gli family of transcription factors that function either as repressors, or as transcription activators according to the HH activation state...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887094/salvianolic-acids-for-injection-safi-promotes-functional-recovery-and-neurogenesis-via-sonic-hedgehog-pathway-after-stroke-in-mice
#19
Ye Zhang, Xiangjian Zhang, Lili Cui, Rong Chen, Cong Zhang, Yaoru Li, Tingting He, Xingyuan Zhu, Zuyuan Shen, Lipeng Dong, Jingru Zhao, Ya Wen, Xiufen Zheng, Pan Li
There is a pressing need of developing approaches for delayed post-stroke therapy for patients who fail to receive thrombolysis within the narrow time window. Neuroprotection of Salvianolic Acids for Injection (SAFI) for cerebral ischemia-reperfusion injury in acute phase has been well documented. The current study was to determine the influence of SAFI at the subacute phase after stroke in mice, and to elucidate the underlying mechanisms. Adult male C57BL/6 mice were subjected to permanent occlusion of the distal middle cerebral artery (dMCAO), followed by daily intraperitoneal injection of SAFI 24 h after stroke for 14 days...
September 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28886322/carnosol-inhibits-hedgehog-signaling-pathway-in-both-lncap-and-du145-prostate-cancer-cell-lines
#20
H Gao, Q Song, J Yang, S Yu, J Zhao, G Yu
To investigate the effect of carnosol on the Hedgehog (HH) signaling pathway in human hormone-dependent prostate cancer cell line LNCaP and hormone-independent prostate cancer cell line DU145. The expression levels of glioma-associated oncogene homolog 1 (Gli1) and Sonic hedgehog (Shh) in human prostate cancer tissues were detected by immunohistochemistry. After treated with carnosol (0.25-16 μmol/L), the cell survival of LNCaP and DU145 cells were detected by MTT assay. The expression levels of Gli1 and Shh mRNA and protein in the two cells were detected by qRT-PCR and western blot, respectively...
August 30, 2017: Cellular and Molecular Biology
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