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Gregory J Logan, Margaret C Wright, Adam C Kubicki, Stephen M Maricich
Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin...
December 11, 2017: Developmental Biology
Shujie Jiao, Yaling Liu, Yaobing Yao, Junfang Teng
Background: Neural stem cells (NSCs) are able to differentiate into neurons and astroglia. miRNAs have been demonstrated to be involved in NSC self-renewal, proliferation and differentiation. However, the exact role of miR-124 in the development of NSCs and its underlying mechanism remain to be explored. Methods: Primary NSCs were isolated from embryos of Wistar rats. Immunocytochemistry was used to stain purified NSCs. miR-124, Delta-like 4 (DLL4), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), HES1, HEY2, and cyclin D1 (CCND1) expressions were detected by qRT-PCR and western blot...
2017: Cell & Bioscience
Weifeng Lu, Xiaoli Chen, Yi Si, Shichai Hong, Zhengyu Shi, Weiguo Fu
Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α ) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P < 0...
2017: Stem Cells International
Xuxiang Sheng, Xiaoyan Zuo, Xihui Liu, Yang Zhou, Xia Sun
PURPOSE: IgA nephropathy (IgAN) is an immune complex-mediated disease involved in the kidney disease. Recent studies have revealed that Notch signaling-related genes are aberrantly expressed in various cell types and maybe associate with inflammation-induced carcinogenesis. The aim of our study was to investigate the function of Notch1 in the inflammatory response of IgAN. METHODS: The expression of Notch1, Jagged1 and NICD1 in 52 IgAN renal tissues and 20 control renal tissues was first determined using quantitative real-time PCR and Western blot...
December 11, 2017: International Urology and Nephrology
Shyam Kumar Gudey, Reshma Sundar, Carl-Henrik Heldin, Anders Bergh, Marene Landström
Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT) during embryogenesis and in tumors. The effect of TGFβ, on ΕΜΤ, is conveyed by induction of the pro-invasive transcription factor Snail1. In this study, we report that TGFβ stimulates Snail1 sumoylation in aggressive prostate, breast and lung cancer cells. Sumoylation of Snail1 lysine residue 234 confers its transcriptional activity, inducing the expression of classical EMT genes, as well as TGFβ receptor I (TβRI) and the transcriptional repressor Hes1...
November 17, 2017: Oncotarget
Lijun Wang, Qi Wu, Shan Zhu, Zhiyu Li, Jingping Yuan, Dehua Yu, Zhiliang Xu, Juanjuan Li, Shengrong Sun, Changhua Wang
DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The function of DNER in prostate cancer has not been evaluated. Here, we showed that the upregulation of DNER is observed in various cancers, including prostate cancer. Knockdown of DNER in PC-3 cells inhibited cell proliferation, migration and invasion as well as tumorigenesis in PC-3 xenografts. DNER knockdown specifically inhibited cell growth in spheroids...
2017: American Journal of Translational Research
Da Gao, Zhen Xiao, Hui-Ping Li, Dong-Hai Han, Ya-Peng Zhang
Although many efforts have contributed to improve our knowledge of molecular pathogenesis about multiple myeloma (MM), the role and significance of microRNAs and long noncoding RNAs in MM cells, along with the core mechanism remains virtually absent. The mRNA levels of miR-125b and MALAT1 in MM cell lines were detected by qRT-PCR. The influence of Lenti-Sh-miR-125b on cell viability and the Notch-1 pathway-related proteins were assessed by MTT method and western blot, respectively. We also investigated the regulation effect between MALAT1 and Notch1 pathway...
December 7, 2017: Cancer Medicine
Mboya Doffou, George Adams, William C Bowen, Shirish Paranjpe, Harish S Parihar, Huy Nguyen, George K Michalopoulos, Vishakha Bhave
BACKGROUND: Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, if Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. METHODS: We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation...
December 6, 2017: Gene Expression
Xing-Li Liu, Gang Wang, Wei Song, Wei-Xin Yang, Jian Hua, Liang Lyu
Cerebral ischemic stroke (CIS) is one of the common causes of death and disability worldwide. This study aims to investigate effect of miR-137 on endothelial progenitor cells and angiogenesis in CIS by targeting NR4A2 via the Notch pathway. Brain tissues were extracted from CIS and normal mice. Immunohistochemistry was used to determine positive rate of NR4A2 expression. Serum VEGF, Ang, HGF and IκBα levels were determined by ELISA. RT-qPCR and western blotting were used to determine expression of related factors...
December 5, 2017: Journal of Cellular Physiology
Natarajan Valliyammai, Nirmala K Nancy, Tenali G Sagar, Thangarajan Rajkumar
NOTCH1/FBXW7 mutations trigger oncogenic NOTCH1 signaling and its downstream target genes play crucial roles in the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). In the present study, NOTCH1 and FBXW7 mutations were studied in 25 primary T-ALL samples. All 34 exons of NOTCH1 and hotspot exons (exon 9 and exon 10) of FBXW7 were polymerase chain reaction amplified and sequenced for mutations. Our results showed that 13/25 (52%) were NOTCH1-mutated, of which 11 patients (44%) showed mutation in the hotspot exons...
December 1, 2017: Journal of Pediatric Hematology/oncology
S Z Zhang, L Cai, B Li
OBJECTIVE: This study aimed to investigate the role of long non-coding RNA MEG3 (lncRNA MEG3) in osteosarcoma (OS) and further explore the underlying molecular mechanism. MATERIALS AND METHODS: The expression profiles of MEG3 in OS cell lines and normal osteoblast cell line were detected by qRT-PCR. MEG3 was over-expressed in OS cell line by using LV-MEG3. MTT and colony-formation assays were applied for cell proliferation analysis. Cell migration assay was applied to investigate the cell migration ability...
2017: Bratislavské Lekárske Listy
Dola Sengupta, Sandip Kar
In the central nervous system, expression level of transcriptional repressor Hes1 (hairy and enhancer of split-1) tightly controls the alternative cell fate commitment during differentiation as well as the time required for such cellular transitions. A microRNA, miR-9 that interacts with Hes1 in a mutually antagonistic manner, influences both the process of lineage specification and timing of differentiation significantly but the impact of the miR-9 in guiding these events still remains poorly understood. Here we proposed a stochastic mathematical model of miR-9/Hes1 double negative feedback interaction network that at the outset shows how alternative cell fate such as quiescence, progenitor and neuronal states can be accomplished through fine-tuning the Hes1 dynamics by altering the expression level of miR-9...
November 28, 2017: ACS Chemical Neuroscience
Ylenia Capodanno, Floryne O Buishand, Lisa Y Pang, Jolle Kirpensteijn, Jan A Mol, David J Argyle
Insulinomas (INS) are the most common neuroendocrine pancreatic tumours in humans and dogs. The long-term prognosis for malignant INS is still poor due to a low success rate of the current treatment modalities, particularly chemotherapy. A better understanding of the molecular processes underlying the development and progression of INS is required to develop novel targeted therapies. Cancer stem cells (CSCs) are thought to be critical for the engraftment and chemoresistance of many tumours, including INS. This study was aimed to characterise and target INS CSCs in order to develop novel targeted therapies...
November 24, 2017: Endocrine-related Cancer
Kai-Hong Wu, Qian-Ru Xiao, Yu Yang, Jia-Li Xu, Feng Zhang, Chao-Ming Liu, Zhao-Ming Zhang, Ying-Qi Lu, Ning-Ping Huang
The objective of the study was to elucidate the mechanism by which microRNA-34a (miR-34a) influences heart development and participates in the pathogenesis of congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling pathway. Forty D7 pregnant mice were recruited for the purposes of the study and served as the CHD (n=20, successfully established as CHD model) and normal (n=20) groups. The positive expression of the NOTCH-1 protein was evaluated by means of immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups...
November 21, 2017: Journal of Molecular and Cellular Cardiology
Jing-Wen Zhang, Ru Yan, Yu-Sheng Tang, Yong-Zhen Guo, Yue Chang, Li Jing, Yi-Li Wang, Jian-Zhong Zhang
It has been reported that hyperhomocysteinemia (HHcy) is associated with neurodegenerative and cardiovascular diseases. However, little is known about brain histomorphology, neuronal organelles, and hairy enhancer of split ( hes) expression under HHcy. In this study, non-HHcy and HHcy induced by high-methionine diet in apolipoprotein E-deficient (Apo E-/-) mice were comparatively investigated. The histomorphology, ultrastructure, autophagosomes, apoptosis, and expression of proteins, HES1, HES5 and P62, were designed to assess the effects of HHcy on brain...
November 1, 2017: International Journal of Immunopathology and Pharmacology
Hongwei Zhao, Che Nan Xu, Chao Huang, Jinzhi Jiang, Liangchang Li
Objective To study the effect of Notch1 signaling on the release of inflammatory mediators in lipopolysaccharide (LPS)-induced macrophages and the related mechanism. Methods The expressions of Notch1 and hairy and enhancer of split 1 (Hes1) mRNAs were investigated by reverse transcription PCR (RT-PCR) in mouse RAW264.7 cells after stimulated with 100 ng/mL LPS for 8 hours. Prior to stimulation with LPS, mouse RAW264.7 cells were treated with DAPT (10 μmol/L), an inhibitor of Notch1 signaling, for 1 hour. The concentrations of tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO) and prostaglandin E2 (PGE2) in cell culture media were measured by ELISA...
October 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Ryu Okada, Megumi Fujimagari, Eri Koya, Yoshikazu Hirose, Tomomi Sato, Yukio Nishina
Stable and sustainable spermatogenesis is supported by the strict regulation of self-renewal and differentiation of spermatogonial stem cells (SSC), which are a rare population of undifferentiated spermatogonia. It has been revealed that some signaling factors regulate the self-renewal of SSC; however, the molecular mechanism of SSC maintenance is still not completely understood. Notch signaling is an evolutionarily conserved juxtacrine signaling that plays important roles in the cell fate determination of various tissue stem cells...
January 22, 2017: Cells, Tissues, Organs
Mi Joung Kim, A-Ram Kim, Ju-Yeon Jeong, Kwang-Il Kim, Tae-Heon Kim, Chan Lee, Kwanghoe Chung, Young-Hyeh Ko, Hee-Jung An
Purpose : ALDH1 is a putative cancer stem cell marker, while the Notch signaling pathway is involved in regulation of cancer stem cell (CSC)s. This study aims to determine the expression of Notch signaling genes in ovarian CSCs, and to assess the clinical impact of expression of ALDH1 and Notch signaling genes in ovarian cancers. Methods : We examined expression of Notch signaling genes in FACS-sorted ALDH1(+) putative ovarian CSCs and expression of ALDH1 and Notch signaling genes in 86 ovarian epithelial tumors and various ovarian cancer cell lines by real-time RT-PCR, including Notch receptors (Notch1-4), Notch ligands (Jagged1 and Jagged2), and the downstream molecule, Hes1...
2017: Journal of Cancer
Yasen Aimaiti, Xin Jin, Wei Wang, Zixin Chen, Dewei Li
AIMS: We tested whether transforming growth factor β1 (TGF-β1) signaling plays an important role in hepatic stellate cell differentiation fate and investigated the role of Jagged1/Notch in this process. MATERIALS AND METHODS: TGF-β1 was overexpressed and transforming growth factor receptor 1 (TGF-β-R1) was knocked down by a lentiviral vector in mouse hepatic stellate cells (mHSCs). Transfection efficiency was assessed with immunofluorescence, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and western blotting...
November 14, 2017: Life Sciences
Wen-Cheng Chung, Junqing Wang, Yunyun Zhou, Keli Xu
Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context. Methods: We determined Cre recombination activity of Pdx1-Cre in the gallbladder using a reporter strain and examined gallbladder tumor development in the Kras(LSL- G12D/+);Pdx1-Cre mice...
September 2017: Oncoscience
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