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C-kit AND SCF

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https://www.readbyqxmd.com/read/28299766/increased-level-of-c-kit-in-semen-of-infertile-patients-with-varicocele
#1
Guorong Jin, Jianrong Liu, Qin Qin, Songdan Gao, Fang Zhang, Yuehong Ma, Caiyun Ding, Lina Dong, Haizhen Yin, Yimin Wang
PURPOSE: Varicocele is the most common risk factor for male infertility, however, not all males with varicocele experience infertility. In fact, most patients with varicocele have normal spermatogenesis. The molecular mechanism of varicocele-associated infertility is yet to be completely understood. The aim of this study is to assess the association of a number of fertility regulatory factors on varicocele associated infertility and to throw light on the mechanism of varicocele-associated infertility...
March 16, 2017: Urology Journal
https://www.readbyqxmd.com/read/28283060/decoupling-the-functional-pleiotropy-of-stem-cell-factor-by-tuning-c-kit-signaling
#2
Chia Chi M Ho, Akanksha Chhabra, Philipp Starkl, Peter-John Schnorr, Stephan Wilmes, Ignacio Moraga, Hye-Sook Kwon, Nicolas Gaudenzio, Riccardo Sibilano, Tom S Wehrman, Milica Gakovic, Jonathan T Sockolosky, Matthew R Tiffany, Aaron M Ring, Jacob Piehler, Irving L Weissman, Stephen J Galli, Judith A Shizuru, K Christopher Garcia
Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28261209/gm-csf-inhibits-c-kit-and-scf-expression-by-bone-marrow-derived-dendritic-cells
#3
Amairelys Belen Barroeta Seijas, Sonia Simonetti, Sara Vitale, Daniele Runci, Angela Caterina Quinci, Alessandra Soriani, Mattia Criscuoli, Irene Filippi, Antonella Naldini, Federico Maria Sacchetti, Umberto Tarantino, Francesco Oliva, Eleonora Piccirilli, Angela Santoni, Francesca Di Rosa
Stem cell factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells, and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28260860/antiproliferation-effect-of-imatinib-mesylate-on-mcf7-t-47d-tumorigenic-and-mcf-10a-nontumorigenic-breast-cell-lines-via-pdgfr-%C3%AE-pdgf-bb-c-kit-and-scf-genes
#4
Ali Kadivar, Behnam Kamalidehghan, Hamid Akbari Javar, Benyamin Karimi, Reihaneh Sedghi, Mohamed Ibrahim Noordin
Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28235674/thrombopoietin-contributes-to-the-formation-and-the-maintenance-of-hematopoietic-progenitor-containing-cell-clusters-in-the-aorta-gonad-mesonephros-region
#5
Kaho Harada, Ikuo Nobuhisa, Maha Anani, Kiyoka Saito, Tetsuya Taga
In the midgestation mouse embryo, hematopoietic cell clusters containing hematopoietic stem/progenitor cells arise in the aorta-gonad-mesonephros (AGM) region. We have previously reported that forced expression of the Sox17 transcription factor in CD45(low)c-Kit(high) AGM cells, which are the hematopoietic cellular component of the cell clusters, and subsequent coculture with OP9 stromal cells in the presence of three cytokines, stem cell factor (SCF), interleukin-3 (IL-3), and thrombopoietin (TPO), led to the formation and the maintenance of cell clusters with cells at an undifferentiated state in vitro...
February 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28181402/allethrin-toxicity-causes-reproductive-dysfunction-in-male-rats
#6
Golla Madhubabu, Suresh Yenugu
Pyrethroids are widely used for domestic and agricultural purposes and their use is increasing, especially in developing countries. Uncontrolled use of these insecticides resulted in their entry into the food chain thereby causing toxicity to different organ systems. Allethrin is one of the widely used pyrethroids, but its toxicological effects are underreported when compared to other pyrethroids. Further, its effects on the male reproductive tract remain uncharacterized. In this study, its toxicity on the male reproductive tract was evaluated by administering 25-150 mg/kg body weight allethrin to adult rats for 60 days...
February 9, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28164252/snap-tag-technology-a-promising-tool-for-ex-vivo-immunophenotyping
#7
Swati Choudhary, Stefan Barth, Rama S Verma
BACKGROUND: SNAP-tag, a self-labeling protein tag, is commonly used for in vitro and in vivo analysis of bound target proteins. We report the first evidence that SNAP-tag could be used for ex vivo detection of enriched biological markers. METHODS: Proof of concept was established for target c-kit receptor, a pathological and diagnostic marker for a variety of cancers. SNAP-tag conjugates with stem-cell factor (SCF) fusion proteins were designed and their binding and specificity was validated in vitro using flow cytometry and immunostaining...
February 6, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28045993/change-in-the-interstitial-cells-of-cajal-and-nnos-positive-neuronal-cells-with-aging-in-the-stomach-of-f344-rats
#8
Yong Hwan Kwon, Nayoung Kim, Ryoung Hee Nam, Ji Hyun Park, Sun Min Lee, Sung Kook Kim, Hye Seung Lee, Yong Sung Kim, Dong Ho Lee
The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28009085/protein-tyrosine-phosphatase-prl2-mediates-notch-and-kit-signals-in-early-t-cell-progenitors
#9
Michihiro Kobayashi, Sarah C Nabinger, Yunpeng Bai, Momoko Yoshimoto, Rui Gao, Sisi Chen, Chonghua Yao, Yuanshu Dong, Lujuan Zhang, Sonia Rodriguez, Yumi Yashiro-Ohtani, Warren S Pear, Nadia Carlesso, Mervin C Yoder, Reuben Kapur, Mark H Kaplan, Hugo Daniel Lacorazza, Zhong-Yin Zhang, Yan Liu
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/27890784/identifying-residues-that-determine-scf-molecular-level-interactions-through-a-combination-of-experimental-and-in-silico-analyses
#10
Eitan Rabinovich, Michael Heyne, Anna Bakhman, Mickey Kosloff, Julia M Shifman, Niv Papo
The stem cell factor (SCF)/c-Kit receptor tyrosine kinase complex-with its significant roles in hematopoiesis and angiogenesis-is an attractive target for rational drug design. There is thus a need to map, in detail, the SCF/c-Kit interaction sites and the mechanisms that modulate this interaction. While most residues in the direct SCF/c-Kit binding interface can be identified from the existing crystal structure of the complex, other residues that affect binding through protein unfolding, intermolecular interactions, allosteric or long-distance electrostatic effects cannot be directly inferred...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27872880/data-on-quantification-of-signaling-pathways-activated-by-kit-and-pdgfra-mutants
#11
Christelle Bahlawane, Martine Schmitz, Elisabeth Letellier, Karthik Arumugam, Nathalie Nicot, Petr V Nazarov, Serge Haan
The present data are related to the article entitled "Insights into ligand stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane, M. Schmitz, E. Letellier, K. Arumugam, N. Nicot, P.V. Nazarov, S. Haan, 2016) [1]. Constitutive and ligand-derived signaling pathways mediated by KIT and PDGFRA mutated proteins found in gastrointestinal stromal tumors (GIST) were compared. Expression of mutant proteins was induced by doxycycline in an isogenic background (Hek293 cells). Kit was identified by FACS at the cell surface and found to be quickly degraded or internalized upon SCF stimulation for both Kit Wild type and Kit mutant counterparts...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27825164/effect-of-neutrophils-on-gallbladder-interstitial-cajal-like-cells-in-guinea-pig-model-of-acute-cholecystitis
#12
Zhen-Peng Huang, Hu Qiu, Yan Yang, Bao-Ping Yu
BACKGROUND: Acute cholecystitis is a common condition in gallbladder motility disorder. Interstitial Cajal-like cells (ICLCs) in the gallbladder are known as one of the players in the complex motility mechanisms affecting gallbladder motility. AIM: This study explored morphological symptoms and molecular mechanisms underlying gallbladder ICLC changes induced by acute cholecystitis. MATERIALS AND METHODS: Fifteen adult guinea pigs were randomly divided into 3 groups: sham-operated group (healthy controls) and 2 experimental groups wherein these guinea pigs were subjected to common bile duct ligation to induce acute cholecystitis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27798921/low-mast-cell-density-predicts-poor-prognosis-in-oral-squamous-cell-carcinoma-and-reduces-survival-in-head-and-neck-squamous-cell-carcinoma
#13
Cecilie Gjøvaag Attramadal, Sheeba Kumar, Jian Gao, Morten Ebbe Boysen, Trond Sundby Halstensen, Magne Bryne
BACKGROUND: The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCs) may reflect biologically important cancer features and host responses, and thus be related to disease progression. The TME density of mast cells (MCs), macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells were quantified at the invasive front and analyzed regarding their relation to disease recurrence in patients with small T1/2N0M0 OSCCs...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27782131/in-vivo-correction-of-anaemia-in-%C3%AE-thalassemic-mice-by-%C3%AE-pna-mediated-gene-editing-with-nanoparticle-delivery
#14
Raman Bahal, Nicole Ali McNeer, Elias Quijano, Yanfeng Liu, Parker Sulkowski, Audrey Turchick, Yi-Chien Lu, Dinesh C Bhunia, Arunava Manna, Dale L Greiner, Michael A Brehm, Christopher J Cheng, Francesc López-Giráldez, Adele Ricciardi, Jagadish Beloor, Diane S Krause, Priti Kumar, Patrick G Gallagher, Demetrios T Braddock, W Mark Saltzman, Danith H Ly, Peter M Glazer
The blood disorder, β-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the γ position plus stimulation of the stem cell factor (SCF)/c-Kit pathway yielded high levels of gene editing in haematopoietic stem cells (HSCs) in a mouse model of human β-thalassaemia. Injection of thalassemic mice with SCF plus nanoparticles containing γPNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, reversal of splenomegaly and up to 7% β-globin gene correction in HSCs, with extremely low off-target effects...
October 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27707610/aberrant-expressions-of-stem-cell-factor-c-kit-in-rat-testis-with-varicocele
#15
Qin Qin, Jianrong Liu, Yuehong Ma, Yimin Wang, Fang Zhang, Songdan Gao, Lina Dong
BACKGROUND/PURPOSE: Varicocele (VC) is considered by the World Health Organization as the main cause of male infertility. Studies have shown that VC can affect spermatogenesis and then result in male infertility. But the exact mechanism by which VC affects spermatogenesis is still unclear. Stem cell factor (SCF) and c-KIT receptor are crucial molecules during spermatogenesis in testis. This study aims to investigate whether SCF/c-KIT signaling is involved in the pathophysiology of VC on spermatogenesis...
October 2, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/27606906/positive-oct-3-4-and-d2-40-immunohistochemical-expression-in-germ-cells-and-suspected-histology-pattern-of-intratubular-germ-cell-neoplasia-in-boys-with-cryptorchidism-vanish-after-the-age-of-2-years
#16
Jorgen Thorup, Erik Clasen-Linde, Dina Cortes
Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy...
September 8, 2016: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/27539014/enhanced-hematopoietic-stem-cell-self-renewal-promoting-ability-of-clonal-primary-mesenchymal-stromal-stem-cells-versus-their-osteogenic-progeny
#17
Qiling He, Claude Scott Swindle, Chao Wan, Robert J Flynn, Robert A Oster, Dongquan Chen, Fengjie Zhang, Yinglan Shu, Christopher A Klug
Long-term self-renewing hematopoietic stem cell (LT-HSC) homeostasis within the bone marrow (BM) of adult mammals is regulated by complex interactions between LT-HSC and a number of niche-associated cell types including mesenchymal stromal/stem cells (MSC), osteoblasts (OB), macrophage, and neuronal cells in close proximity with the vasculature. Here, we cloned and functionally characterized a murine BM MSC subpopulation that was uniformly Nestin(+) Lepr (+) Sca-1(+) CD146(+) and could be stably propagated with high colony-forming unit fibroblast re-cloning efficiency...
August 19, 2016: Stem Cells
https://www.readbyqxmd.com/read/27478893/total-glucosides-of-paeony-promote-intestinal-motility-in-slow-transit-constipation-rats-through-amelioration-of-interstitial-cells-of-cajal
#18
Feiye Zhu, Shan Xu, Yongsheng Zhang, Fangming Chen, Jinjun Ji, Guanqun Xie
OBJECTIVES: Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms. STUDY DESIGN: A prospective experimental animal study. METHODS: The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated...
2016: PloS One
https://www.readbyqxmd.com/read/27451973/a-novel-slug-containing-negative-feedback-loop-regulates-scf-c-kit-mediated-hematopoietic-stem-cell-self-renewal
#19
Z Zhang, P Zhu, Y Zhou, Y Sheng, Y Hong, D Xiang, Z Qian, J Mosenson, W-S Wu
The stem cell factor (SCF)/c-Kit pathway has crucial roles in controlling hematopoietic stem cell (HSC) renewal. However, little is known about the intracellular regulation of the SCF/c-Kit pathway in HSCs. We report here that Slug, a zinc-finger transcription repressor, functions as a direct transcriptional repressor of c-Kit in HSCs. Conversely, SCF/c-Kit signaling positively regulates Slug through downstream c-Myc and FoxM1 transcription factors. Intriguingly, c-Kit expression is induced by SCF/c-Kit signaling in Slug-deficient HSCs...
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27451100/molecular-signaling-pathways-controlling-vascular-tube-morphogenesis-and-pericyte-induced-tube-maturation-in-3d-extracellular-matrices
#20
S L K Bowers, P R Norden, G E Davis
During capillary network formation, ECs establish interconnecting tubes with defined lumens that reside within vascular guidance tunnels (physical spaces generated during EC tubulogenesis). Pericytes are recruited to EC tubes within these tunnels and capillary basement membrane deposition occurs to facilitate tube maturation. Here, we discuss molecular mechanisms controlling EC tubulogenesis demonstrating the involvement of integrins, MT1-MMP, extracellular matrix, Cdc42, Rac1, Rac2, k-Ras, Rap1b, and key downstream effectors including Pak2, Pak4, IQGAP1, MRCKβ, and Rasip1...
2016: Advances in Pharmacology
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