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Girak Kim, Min Jeong Gu, Soo Ji Kim, Kwang Hyun Ko, Yoon-Chul Kye, Cheol Gyun Kim, Jae-Ho Cho, Woon-Kyu Lee, Ki-Duk Song, Hyuk Chu, Yeong-Min Park, Seung Hyun Han, Cheol-Heui Yun
γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27- γδ T (γδ27- -17) cells. We found selective augmentation of Vγ4+ γδ27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27- -17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli...
2018: Frontiers in Immunology
Joseph X DiMario
Dystrophic skeletal muscle is characterized by fibrotic accumulation of extracellular matrix components that compromise muscle structure, function, and capacity for regeneration. Tissue fibrosis is often initiated and sustained through transforming growth factor β (TGFβ) signaling, and KLF10 is an immediate early gene that is transcriptionally activated in response to TGFβ signaling. It encodes a transcriptional regulator that mediates the effects of TGFβ signaling in a variety of cell types. This report presents results of investigation of the effects of loss of KLF10 gene expression in wild-type and dystrophic (mdx) skeletal muscle...
February 16, 2018: American Journal of Pathology
Xilin Zhang, Yi Yao, Wei-Zen Wei, Zeng-Quan Yang, Jun Gu, Li Zhou
TGF-β-inducible early gene 1 (TIEG1), also known as Krüppel-like factor 10 (Klf10), represents a major downstream transcription factor of transforming growth factor-β1 (TGF-β1) signaling. Epidermal Langerhans cells (LCs), a unique subpopulation of dendritic cells (DC), essentially mediates immune surveillance and tolerance. TGF-β1 plays a pivotal role in LC maintenance and function after birth, although the underpinning mechanisms remain elusive. Here, we hypothesized that TIEG1 might be involved in TGF-β1-mediated LC homeostasis and function...
December 22, 2017: Oncotarget
J Bouvier-Muller, C Allain, F Enjalbert, Y Farizon, D Portes, G Foucras, R Rupp
During the transition from late gestation to early lactation ruminants experience a negative energy balance (NEB), which is considered to increase susceptibility to mammary infections. Our previous study in 2 divergent lines of sheep selected for high and low somatic cell score (SCS) suggested an association between the response to NEB and genetic susceptibility to mastitis. Forty-eight early-lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2 homogeneous subgroups-an NEB group, which was energy restricted and received 60% of the energy requirements for 15 d, and a control-fed group-to obtain 4 balanced groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy balance, high-SCS NEB, and low-SCS NEB...
January 10, 2018: Journal of Dairy Science
Su Yu, Feng Wang, Xiao Tan, Guo-Li Gao, Wei-Juan Pan, Yi Luan, Xin Ge
FBW7, a key component of SCFFBW7 E3 ubiquitin ligase, targets various proteins for degradation via the conserved Cdc4 phosphodegron (CPD) in substrates. In this study, we report that KLF10 is degraded by FBW7 via a conserved CPD. Through systematic analysis of the degradation of KLF transcription factors by FBW7, we identified KLF10 as a novel degradation target of FBW7. Ectopic expression of FBW7 markedly promoted the degradation of KLF10 while knockdown of endogenous FBW7 increased the protein levels of KLF10...
January 8, 2018: Biochemical and Biophysical Research Communications
Sun-Hee Ahn, Seongmin Chun, Chungoo Park, Jong-Hee Lee, Seok-Woo Lee, Tae-Hoon Lee
Periodontal disease is caused by dental plaque biofilms. Fusobacterium nucleatum is an important periodontal pathogen involved in the development of bacterial complexity in dental plaque biofilms. Human gingival fibroblasts (GFs) act as the first line of defense against oral microorganisms and locally orchestrate immune responses by triggering the production of reactive oxygen species and pro-inflammatory cytokines (IL-6 and IL-8). The frequency and severity of periodontal diseases is known to increase in elderly subjects...
2017: PloS One
Lingying Meng, Muting Wang, Zepeng Du, Zhongmin Fang, Bingli Wu, Jianyi Wu, Wenming Xie, Jian Shen, Tianxiang Zhu, XieE Xu, Liandi Liao, Liyan Xu, Enmin Li, Bin Lan
LCN2 is involved in various cellular functions, including transport of small hydrophobic molecules, protection of MMP9 from proteolytic degradation, and regulating innate immunity. LCN2 is elevated in multiple human cancers, frequently being associated with tumor size, stage, and invasiveness. Our previous studies have shown that LCN2 expression could be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in esophageal squamous cell carcinoma (ESCC) by the binding of five nucleoproteins (MISP, KLF10, KLF15, PPP1R18, and RXRβ) at a novel TPA-responsive element (TRE), at -152~-60 bp of the 5' flanking region of the LCN2 promoter...
2017: BioMed Research International
Kaikai Wu, Zhiying Jia, Qi'ai Wang, Zhenlin Wei, Zunchun Zhou, Xiaolin Liu
Accumulating evidence indicates that Krüppel-like factors (KLFs) play important roles in fat biology via the regulation of CCAAT/enhancer binding proteins (C/EBPs). However, KLFs and C/EBPs have not been identified from Strongylocentrotus nudus, and their roles in this species are not clear. In this study, the full-length cDNA of S. nudus KLF10 (SnKLF10) and three cDNA fragments of S. nudus C/EBPs (SnC/EBPs) were obtained. Examination of tissue distribution and expression patterns during gonadal development implied that SnKLF10 and SnC/EBPs play important roles in gonadal lipogenesis...
October 2017: Genome Génome / Conseil National de Recherches Canada
Xiaoying Yang, Qi Chen, Lihong Sun, Huabing Zhang, Lu Yao, Xiaona Cui, Yong Gao, Fude Fang, Yongsheng Chang
AIM/HYPOTHESIS: Abnormal activation of hepatic gluconeogenesis leads to hyperglycaemia. However, the molecular mechanisms underlying dysregulated hepatic gluconeogenesis remain to be fully defined. Here, we explored the physiological role of Krüppel-like factor 10 (KLF10) in regulating hepatic glucose metabolism in mice. METHODS: Hepatic KLF10 expression in wild-type C57BL/6J mice, the db/db mouse model of diabetes, the ob/ob mouse model of obesity and high-fat-diet-induced obese (DIO) mice was measured...
December 2017: Diabetologia
Nan Yang, Jinqiu Chen, Hui Zhang, Xiaman Wang, Huan Yao, Yue Peng, Wanggang Zhang
Numerous studies confirmed that aberrant miRNAs expression contributes to multiple myeloma (MM) development and progression. However, the roles of specific miRNAs in MM remain to be investigated. In present study, we demonstrated that miR-410 expression was increased in MM newly diagnosed and relapsed tissues and cell lines. Clinical analysis revealed that miR-410 was positively correlated with advanced ISS stage. Moreover, high miR-410 expression in MM patients showed an obvious shorter overall survival and progression-free survival...
August 10, 2017: Cell Death & Disease
Seung-Ho Heo, Eui-Suk Jeong, Kyoung-Sun Lee, Jin-Hee Seo, Woon-Kyu Lee, Yang-Kyu Choi
The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice...
June 2017: Oncology Letters
C-C Weng, J R Hawse, M Subramaniam, V H S Chang, W C Y Yu, W-C Hung, L-T Chen, K-H Cheng
Krüppel-like transcription factor 10 (KLF10), also named as TIEG1, plays essential roles in mediating transforming growth factor beta (TGFβ) signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer progression in vivo have yet to be fully characterized. Here, we have employed two well-characterized Pdx-1CreLSL-Kras(G12D) and Pdx-1CreLSL-Kras(G12D)p53(L/L) pancreatic cancer models to ablate KLF10 expression and determine the impact of KLF10 deletion on tumor development and progression...
September 28, 2017: Oncogene
Joanna Budna, Artur Bryja, Piotr Celichowski, Wiesława Kranc, Sylwia Ciesiółka, Sylwia Borys, Marta Rybska, Agata Kolecka-Bednarczyk, Michal Jeseta, Dorota Bukowska, Paweł Antosik, Klaus P Brüssow, Małgorzata Bruska, Michał Nowicki, Maciej Zabel, Bartosz Kempisty
Mammalian cumulus-oocyte complexes (COCs) reach full developmental capability during folliculogenesis and oogenesis. It is well recognized that only gametes achieving MII stage after in vivo or in vitro maturation (IVM) are successfully fertilized by a single spermatozoon. Although the process of oocyte nuclear and/or cytoplasmic maturation in pigs is well determined, there exist many differences that promote these processes in vivo and in vitro. Therefore, this study aimed to investigate the differences in RNA expression profiles between porcine oocytes before and after IVM using microarray and real-time quantitative polymerase chain reaction (RT-qPCR) assays...
August 2017: DNA and Cell Biology
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Shih-Jen Tsai
Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population...
2017: PloS One
Vivek Kumar Mishra, Malayannan Subramaniam, Vijayalakshmi Kari, Kevin S Pitel, Simon J Baumgart, Ryan M Naylor, Sankari Nagarajan, Florian Wegwitz, Volker Ellenrieder, John R Hawse, Steven A Johnsen
TGFβ-SMAD signaling exerts a contextual effect that suppresses malignant growth early in epithelial tumorigenesis but promotes metastasis at later stages. Longstanding challenges in resolving this functional dichotomy may uncover new strategies to treat advanced carcinomas. The Krüppel-like transcription factor, KLF10, is a pivotal effector of TGFβ/SMAD signaling that mediates antiproliferative effects of TGFβ. In this study, we show how KLF10 opposes the prometastatic effects of TGFβ by limiting its ability to induce epithelial-to-mesenchymal transition (EMT)...
May 1, 2017: Cancer Research
Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
BACKGROUND AND PURPOSE: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. MATERIALS AND METHODS: Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay...
March 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Yanliang Zhang, Qiuyue Xue, Guoqing Pan, Qing H Meng, Xiaoyu Tuo, Xuemei Cai, Zhenghui Chen, Ya Li, Tao Huang, Xincen Duan, Yong Duan
OBJECTIVES: Lung cancer in Xuanwei (LCXW), China, is known throughout the world for its distinctive characteristics, but little is known about its pathogenesis. The purpose of this study was to screen potential novel "driver genes" in LCXW. METHODS: Genome-wide DNA copy number alterations (CNAs) were detected by array-based comparative genomic hybridization and differentially expressed genes (DEGs) by gene expression microarrays in 8 paired LCXW and non-cancerous lung tissues...
2017: PloS One
Aikaterini Gravia, Vasiliki Chondrou, Alexandra Kolliopoulou, Alexandra Kourakli, Anne John, Argyris Symeonidis, Bassam R Ali, Argyro Sgourou, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
AIMS: Hemoglobinopathies, particularly β-thalassemia and sickle cell disease, are characterized by great phenotypic variability in terms of disease severity, while notable differences have been observed in hydroxyurea treatment efficacy. In both cases, the observed phenotypic diversity is mostly dependent on the elevated fetal hemoglobin levels, resulting from the persistent fetal globin gene expression in the adult erythroid stage orchestrated by intricate mechanisms that still remain only partly understood...
October 21, 2016: Pharmacogenomics
Malek Kammoun, Philippe Pouletaut, Francis Canon, Malayannan Subramaniam, John R Hawse, Muriel Vayssade, Sabine F Bensamoun
As transforming growth factor (TGF)-β inducible early gene-1 is highly expressed in skeletal muscle, the effect of TIEG1 gene deletion on the passive mechanical properties of slow and fast twitch muscle fibers was analyzed. Twenty five muscle fibers were harvested from soleus (Sol) and extensor digitorum longus (EDL) muscles from TIEG1-/- (N = 5) and control (N = 5) mice. Mechanical tests were performed on fibers and the dynamic and static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data...
2016: PloS One
Liang-Ti Huang, Hsuen-Wen Chang, Min-Ju Wu, Yong-Tzuo Lai, Wen-Chi Wu, Winston C Y Yu, Vincent H S Chang
KLF10 is a transforming growth factor (TGF)-β/Smad downstream regulated gene. KLF10 binds to the promoter of target genes and mimics the effects of TGF-β as a transcriptional factor. In our laboratory, we noted that Klf10 deficiency in mice is associated with significant inflammation of the lungs. However, the precise mechanism of this association remains unknown. We previously identified NPRA as a target gene potentially regulated by KLF10 through direct binding; NPRA knockout have known that prevented lung inflammation in a mouse model of allergic asthma...
October 2016: International Journal of Biochemistry & Cell Biology
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