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https://www.readbyqxmd.com/read/28219886/dependence-of-glomerulonephritis-induction-on-novel-intraglomerular-alternatively-activated-bone-marrow-derived-macrophages-and-mac-1-and-pd-l1-in-lupus-prone-nzm2328-mice
#1
Sun-Sang J Sung, Yan Ge, Chao Dai, Hongyang Wang, Shu Man Fu, Rahul Sharma, Young S Hahn, Jing Yu, Thu H Le, Mark D Okusa, Warren K Bolton, Jessica R Lawler
Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead-purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti-glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11b(+)F4/80(-)I-A(-) macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing Klf4, Il10, Retnla, Tnf, and Il6 mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28197636/mir-21-and-klf4-jointly-augment-epithelial%C3%A2-mesenchymal-transition-via-the-akt-erk1-2-pathway
#2
Chen-Hai Liu, Qiang Huang, Zhi-Yuan Jin, Cheng-Lin Zhu, Zhen Liu, Chao Wang
miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected with a hsa-miR-21 antagomir or control vectors. The EMT-related Krüppel-like factor 4 (KLF4) gene was downregulated after miR-21 was knocked down. Overexpression of miR-21 upregulated KLF4, Akt, ERK and mesenchymal cell markers (N-cadherin and vimentin), downregulated the expression of epithelial cell marker E-cadherin and reduced cell migration and invasion...
February 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28193206/inducing-goat-pluripotent-stem-cells-with-four-transcription-factor-mrnas-that-activate-endogenous-promoters
#3
Hao Chen, Qisheng Zuo, Yingjie Wang, Jiuzhou Song, Huilin Yang, Yani Zhang, Bichun Li
BACKGROUND: Traditional approaches for generating goat pluripotent stem cells (iPSCs) suffer from complexity and low preparation efficiency. Therefore, we tried to derive goat iPSCs with a new method by transfecting exogenous Oct4, Sox2, Klf4 and c-Myc mRNAs into goat embryonic fibroblasts (GEFs), and explore the mechanisms regarding the transcription regulation of the reprogramming factors in goat iPSCs induction. RESULTS: mRNAs of the four reprogramming factors were transfected into GEFs, and were localized in nucleus with approximately 90% transfection efficiency...
February 13, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28192402/loss-of-klf4-and-consequential-downregulation-of-smad7-exacerbate-oncogenic-tgf-%C3%AE-signaling-in-and-promote-progression-of-hepatocellular-carcinoma
#4
H Sun, Z Peng, H Tang, D Xie, Z Jia, L Zhong, S Zhao, Z Ma, Y Gao, L Zeng, R Luo, K Xie
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28181495/expression-of-%C3%AE-globin-by-cancer-cells-promotes-cell-survival-during-blood-borne-dissemination
#5
Yu Zheng, David T Miyamoto, Ben S Wittner, James P Sullivan, Nicola Aceto, Nicole Vincent Jordan, Min Yu, Nezihi Murat Karabacak, Valentine Comaills, Robert Morris, Rushil Desai, Niyati Desai, Erin Emmons, John D Milner, Richard J Lee, Chin-Lee Wu, Lecia V Sequist, Wilhelm Haas, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Shyamala Maheswaran, Daniel A Haber
Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179525/differentiation-dependent-lmp1-expression-is-required-for-efficient-lytic-ebv-reactivation-in-epithelial-cells
#6
Dhananjay M Nawandar, Makoto Ohashi, Reza Djavadian, Elizabeth Barlow, Kathleen Makielski, Ahmed Ali, Denis Lee, Paul F Lambert, Eric Johannsen, Shannon C Kenney
Epstein-Barr virus (EBV)-associated diseases of epithelial cells, including tumors such as nasopharyngeal carcinoma (NPC) that have latent infection, and oral hairy leukoplakia (OHL) lesions that have lytic infection, frequently express the viral latent membrane protein 1 (LMP1). In lytically-infected cells, LMP1 expression is activated by the BRLF1 (R) immediate-early (IE) protein. However, the mechanisms by which LMP1 expression is normally regulated in epithelial cells remain poorly understood, and its potential roles in regulating lytic reactivation in epithelial cells are as yet unexplored...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28170296/muse-cells-derived-from-dermal-tissues-can-differentiate-into-melanocytes
#7
Ting Tian, Ru-Zhi Zhang, Yu-Hua Yang, Qi Liu, Di Li, Xiao-Ru Pan
The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively...
February 7, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28169326/novel-peptides-for-deciphering-structural-and-signalling-functions-of-e-cadherin-in-mouse-embryonic-stem-cells
#8
Joe M Segal, Christopher M Ward
We have previously shown that E-cadherin regulates the naive pluripotent state of mouse embryonic stem cells (mESCs) by enabling LIF-dependent STAT3 phosphorylation, with E-cadherin null mESCs exhibiting over 3000 gene transcript alterations and a switch to Activin/Nodal-dependent pluripotency. However, elucidation of the exact mechanisms associated with E-cadherin function in mESCs is compounded by the difficulty in delineating the structural and signalling functions of this protein. Here we show that mESCs treated with the E-cadherin neutralising antibody DECMA-1 or the E-cadherin binding peptide H-SWELYYPLRANL-NH2 (Epep) exhibit discrete profiles for pluripotent transcripts and NANOG protein expression, demonstrating that the type of E-cadherin inhibitor employed dictates the cellular phenotype of mESCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167653/orai1-activates-proliferation-of-lymphatic-endothelial-cells-in-response-to-laminar-flow-through-kr%C3%A3-ppel-like-factors-2-and-4
#9
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Mingu Hong, Sunju Lee, James Burford, Georgina Gyarmati, Janos Peti-Peterdi, Sonal Srikanth, Yousang Gwack, Chester J Koh, Evgenii Boriushkin, Anne Hamik, Alex K Wong, Young-Kwon Hong
RATIONALE: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown. OBJECTIVE: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation. METHODS AND RESULTS: Primary endothelial cells from dermal blood and lymphatic vessels (BECs and LECs) were exposed to low-rate steady laminar flow...
February 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28167342/cellular-transformation-of-human-mammary-epithelial-cells-by-satb2
#10
Wei Yu, Yiming Ma, Augusto C Ochoa, Sharmila Shankar, Rakesh K Srivastava
Breast tumors are heterogeneous and carry a small population of progenitor cells that can produce various subtypes of breast cancer. SATB2 (special AT-rich binding protein-2) is a newly identified transcription factor and epigenetic regulator. It is highly expressed in embryonic stem cells, but not in adult tissues, and regulates pluripotency-maintaining factors. However, the molecular mechanisms by which SATB2 induces transformation of human mammary epithelial cells (HMECs) leading to malignant phenotype are unknown...
February 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28157205/epex-epcam-and-oct4-or-klf4-alone-are-sufficient-to-generate-induced-pluripotent-stem-cells-through-stat3-and-hif2%C3%AE
#11
I-I Kuan, Kang-Hao Liang, Yi-Ping Wang, Ting-Wen Kuo, Yaa-Jyuhn James Meir, Sareina Chiung-Yuan Wu, Shang-Chih Yang, Jean Lu, Han-Chung Wu
Epithelial cell adhesion molecule (EpCAM) was reported to be cleaved into extracellular domain of EpCAM (EpEX) and intracellular domain of EpCAM (EpICD). We previously reported that EpCAM serves as a potent stem cell marker which is highly and selectively expressed by undifferentiated rather than differentiated hESC. However, the functional role of EpCAM remains elusive. Here, we found that EpEX and EpCAM enhance the efficiency of OSKM reprogramming. Interestingly, Oct4 or Klf4 alone, but not Sox2, can successfully reprogram fibroblasts into iPSCs with EpEX and EpCAM...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155862/synergetic-effects-of-dna-methylation-and-histone-modification-during-mouse-induced-pluripotent-stem-cell-generation
#12
Guiying Wang, Rong Weng, Yuanyuan Lan, Xudong Guo, Qidong Liu, Xiaoqin Liu, Chenqi Lu, Jiuhong Kang
DNA methylation and histone methylation (H3K27me3) have been reported as major barriers to induced pluripotent stem cell (iPSC) generation using four core transcription factors (Oct4, Sox2, Klf4, and c-Myc, termed OSKM). Here, to illustrate the possibility of deriving iPSCs via demethylation, as well as the exact effects of DNA methylation and histone modification on gene expression regulation, we performed RNA sequencing to characterize the transcriptomes of ES cells and iPSCs derived by demethylation with miR-29b or shDnmt3a, and carried out integrated analyses...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28117800/generation-of-integration-free-induced-pluripotent-stem-cells-from-human-peripheral-blood-mononuclear-cells-using-episomal-vectors
#13
Wei Wen, Jian-Ping Zhang, Wanqiu Chen, Cameron Arakaki, Xiaolan Li, David Baylink, Gary D Botimer, Jing Xu, Weiping Yuan, Tao Cheng, Xiao-Bing Zhang
Induced Pluripotent Stem Cells (iPSCs) hold great promise for disease modeling and regenerative therapies. We previously reported the use of Episomal Vectors (EV) to generate integration-free iPSCs from peripheral blood mononuclear cells (PB MNCs). The episomal vectors used are DNA plasmids incorporated with oriP and EBNA1 elements from the Epstein-Barr (EB) virus, which allow for replication and long-term retainment of plasmids in mammalian cells, respectively. With further optimization, thousands of iPSC colonies can be obtained from 1 mL of peripheral blood...
January 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28111071/cooperative-binding-of-transcription-factors-orchestrates-reprogramming
#14
Constantinos Chronis, Petko Fiziev, Bernadett Papp, Stefan Butz, Giancarlo Bonora, Shan Sabri, Jason Ernst, Kathrin Plath
Oct4, Sox2, Klf4, and cMyc (OSKM) reprogram somatic cells to pluripotency. To gain a mechanistic understanding of their function, we mapped OSKM-binding, stage-specific transcription factors (TFs), and chromatin states in discrete reprogramming stages and performed loss- and gain-of-function experiments. We found that OSK predominantly bind active somatic enhancers early in reprogramming and immediately initiate their inactivation genome-wide by inducing the redistribution of somatic TFs away from somatic enhancers to sites elsewhere engaged by OSK, recruiting Hdac1, and repressing the somatic TF Fra1...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28108288/klf4-expression-enhances-the-efficacy-of-chemotherapy-drugs-in-ovarian-cancer-cells
#15
Baojin Wang, Airong Shen, Xuan Ouyang, Guannan Zhao, Ziyun Du, Wenying Huo, Tao Zhang, Yinan Wang, Chuanhe Yang, Peixin Dong, Hidemichi Watari, Lawrence M Pfeffer, Junming Yue
KLF4 is a transcriptional factor that can function either as a tumor suppressor or oncogene in cancer based on its cellular context. We recently demonstrated that KLF4 was a tumor suppressor in ovarian cancer cells by inhibiting the epithelial to mesenchymal transition. Here we report that KLF4 expression was downregulated in ovarian cancer tissue compared to normal ovarian tissue, and low KLF4 expression correlated with high risk ovarian carcinoma and poor patient survival. Enforced KLF4 expression by lentiviral transduction sensitized ovarian cancer cells to the effects of the chemotherapy drugs, paclitaxel and cisplatin...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28104026/-function-and-mechanism-of-zinc-finger-protein-znf50-in-inhibiting-the-growth-of-esophageal-squamous-cell-carcinoma-cells
#16
J Wang, Y H Bi, J Yang, F Liu, Y K Li, H Y Cui, F Wang, J Liu, B Yang, L Zhang
Objective: To investigate the function and mechanism of zinc finger protein 750 (ZNF750) in esophageal squamous cell carcinoma (ESCC). Methods: Xenograft in nude mice was applied to detect the tumorigenesis of ZNF750-depleted ESCC cells. Western blot was performed to observe the expression of downstream target protein of ZNF750 in ESCC cell lines and xenograft tumor tissues in which ZNF750 was knocked down. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay was used to determine the proliferation of ZNF750 stably depleted cells after restoration of its target protein...
January 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#17
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28097234/kruppel-like-factor4-regulates-prdm1-expression-through-binding-to-an-autoimmune-risk-allele
#18
Su Hwa Jang, Helen Chen, Peter K Gregersen, Betty Diamond, Sun Jung Kim
A SNP identified as rs548234, which is found in PRDM1, the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the PRDM1 rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP. KLF4 is highly expressed in MO-DCs but undetectable in B cells, consistent with the lack of altered expression of BLIMP1 in B cells from risk SNP carriers...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28091581/icaritin-enhances-mesc-self-renewal-through-upregulating-core-pluripotency-transcription-factors-mediated-by-er%C3%AE
#19
Wing Pui Tsang, Fengjie Zhang, Qiling He, Waijiao Cai, Jianhua Huang, Wai Yee Chan, Ziyin Shen, Chao Wan
Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of mESCs self-renewal is characterized by increased population in S-phase of cell cycle, elevation of Cylin E and Cyclin-dependent kinase 2 (CDK2) and downregulation of p21, p27 and p57...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28091538/mircorna-145-promotes-activation-of-hepatic-stellate-cells-via-targeting-kr%C3%A3-ppel-like-factor-4
#20
Ruoting Men, Maoyao Wen, Mingyue Zhao, Xuelian Dan, Zongze Yang, Wenchao Wu, Maggie Haitian Wang, Xiaojing Liu, Li Yang
Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-βtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs...
January 16, 2017: Scientific Reports
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