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Diego F Gualtero, Sergio M Viafara-Garcia, Sandra J Morantes, Diana M Buitrago, Octavio A Gonzalez, Gloria I Lafaurie
BACKGROUND: Rosuvastatin exhibits anti-inflammatory effects and reduces periodontal diseases and atherosclerosis; however, its role in regulating periodontopathogen-induced endothelial pro-inflammatory responses remains unclear. The purpose of this study was to determine whether rosuvastatin can reduce the pro-inflammatory response induced by A. actinomycetemcomitans in human coronary artery endothelial cells (HCAECs). METHODS: HCAECs were stimulated with purified A...
October 14, 2016: Journal of Periodontology
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
October 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Xiong Xiao, Nan Li, Dapeng Zhang, Bo Yang, Hongmei Guo, Yuemin Li
Induced pluripotent stem cells (iPSCs) share many characteristics with embryonic stem cells, but lack ethical controversy. They provide vast opportunities for disease modeling, pathogenesis understanding, therapeutic drug development, toxicology, organ synthesis, and treatment of degenerative disease. However, this procedure also has many potential challenges, including a slow generation time, low efficiency, partially reprogrammed colonies, as well as somatic coding mutations in the genome. Pioneered by Shinya Yamanaka's team in 2006, iPSCs were first generated by introducing four transcription factors: Oct 4, Sox 2, Klf 4, and c-Myc (OSKM)...
October 2016: Cellular Reprogramming
Min-Kyung Jang, Sunwoo Lee, Myeong Ho Jung
In this study, we performed high throughput RNA sequencing at the preadipocyte (D0) and differentiated adipocyte (D7) stages of primary brown preadipocyte differentiation in order to characterize the transcriptional events regulating differentiation and function. Compared to the preadipocyte stage (D0), 6,668 genes were identified as differentially expressed genes (DEGs) with a fold change of ≥ 2.0 at the differentiated adipocyte stage (D7). Several adipogenic genes including peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), and Krüppel-like factor (KLF) family genes were differentially expressed at D0 and D7...
2016: PloS One
Changyu Zhou, Jiayu Li, Jiarui Li, Yingchun Wan, Tao Li, Piyong Ma, Yingjian Wang, Haiyan Sang
The aim of the present study was to identify the differentially expressed microRNAs (DEMs) between Lynch syndrome (LS) and the normal colonic (N-C) control samples, predict the target genes (TGs) and analyze the potential functions of the DEMs and TGs. The miRNA expression dataset GSE30454, which included data of 13 LS and 20 N-C tissue samples, was downloaded from the Gene Expression Omnibus. The classical t-test in Linear Models for Microarray Data package was used for DEM identification. TG prediction was performed using 5 databases...
September 2016: Oncology Letters
Neli Kachamakova-Trojanowska, Witold Nowak, Krzysztof Szade, Jacek Stepniewski, Karolina Bukowska-Strakova, Monika Zukowska, Hevidar Taha, Antonina Chmura-Skirlinska, Michael Beilharz, Jozef Dulak, Alicja Jozkowicz
Induced pluripotent stem cells (iPSCs) have shown great potential in regenerative medicine and research applications like disease modeling or drug discovery. Endothelium is indispensable for vascular homeostasis, whereas endothelial dysfunction could lead to different diseases. Therefore, generating autologous cells, able to restore the endothelial lining, can be crucial for slowing or reversing certain pathological processes. In the current study we show efficient differentiation of murine iPSCs into endothelial cells (ECs) with stable CD34+/Tie-2+/Sca-1+/CD45- phenotype and proven functionality...
August 25, 2016: Vascular Pharmacology
S Alaei, A S Knaupp, S M Lim, J Chen, M L Holmes, M L Änkö, C M Nefzger, J M Polo
Reprogrammable mouse models engineered to conditionally express Oct-4, Klf-4, Sox-2 and c-Myc (OKSM) have been instrumental in dissecting molecular events underpinning the generation of induced pluripotent stem cells. However, until now these models have been reported in the context of the m2 reverse tetracycline-controlled transactivator, which results in low reprogramming efficiency and consequently limits the number of reprogramming intermediates that can be isolated for downstream profiling. Here, we describe an improved OKSM mouse model in the context of the reverse tetracycline-controlled transactivator 3 with enhanced reprogramming efficiency (>9-fold) and increased numbers of reprogramming intermediate cells albeit with similar kinetics, which we believe will facilitate mechanistic studies of the reprogramming process...
July 2016: Stem Cell Research
Narges Obeidi, Ali Akbar Pourfathollah, Masoud Soleimani, Mahin Nikougoftar Zarif, Fatemeh Kouhkan
OBJECTIVE: MicroRNAs (miRNAs) are small endogenous non-coding regulatory RNAs that control mRNAs post-transcriptionally. Several mouse stem cells miRNAs are cloned differentially regulated in different hematopoietic lineages, suggesting their possible role in hematopoietic lineage differentiation. Recent studies have shown that specific miRNAs such as Mir-451 have key roles in erythropoiesis. MATERIALS AND METHODS: In this experimental study, murine embryonic stem cells (mESCs) were infected with lentiviruses containing pCDH-Mir-451...
July 2016: Cell Journal
Maddalena Coppo, Yurii Chinenov, Maria A Sacta, Inez Rogatsky
Diet-induced obesity causes chronic macrophage-driven inflammation in white adipose tissue (WAT) leading to insulin resistance. WAT macrophages, however, differ in their origin, gene expression and activities: unlike infiltrating monocyte-derived inflammatory macrophages, WAT-resident macrophages counteract inflammation and insulin resistance, yet, the mechanisms underlying their transcriptional programming remain poorly understood. We recently reported that a nuclear receptor cofactor-glucocorticoid receptor (GR)-interacting protein (GRIP)1-cooperates with GR to repress inflammatory genes...
2016: Nature Communications
Lucía Flores-Peredo, Gabriela Rodríguez, Angel Zarain-Herzberg
The Sarco/Endoplasmic Reticulum Ca(2+) -ATPases (SERCAs), pump Ca(2+) into the endoplasmic reticulum lumen modulating cytosolic Ca(2+) concentrations to regulate various cellular processes including cell growth. Previous studies have reported a downregulation of SERCA3 protein expression in gastric and colon cancer cell lines and showed that in vitro cell differentiation increases its expression. However, little is known about the transcriptional mechanisms and transcription factors that regulate SERCA3 expression in epithelial cancer cells...
July 19, 2016: Molecular Carcinogenesis
Jianbo Wang, Joana Galvao, Krista M Beach, Weijia Luo, Raul A Urrutia, Jeffrey L Goldberg, Deborah C Otteson
Regenerative medicine holds great promise for the treatment of degenerative retinal disorders. Krüppel-like factors (KLFs) are transcription factors that have recently emerged as key tools in regenerative medicine because some of them can function as epigenetic reprogrammers in stem cell biology. Here, we show that KLF16, one of the least understood members of this family, is a POU4F2 independent transcription factor in retinal ganglion cells (RGCs) as early as embryonic day 15. When overexpressed, KLF16 inhibits RGC neurite outgrowth and enhances RGC growth cone collapse in response to exogenous ephrinA5 ligands...
August 26, 2016: Journal of Biological Chemistry
Hirofumi Zempo, Jun-Ichi Suzuki, Masahito Ogawa, Ryo Watanabe, Katsuhito Fujiu, Ichiro Manabe, Simon J Conway, Yoshiaki Taniyama, Ryuichi Morishita, Yasunobu Hirata, Mitsuaki Isobe, Ryozo Nagai
Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Krüppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5(Postn)KO: Klf5(flox/flox); Postn(Cre/-)) and wild-type mice (WT: Klf5(flox/flox); Postn(-/-))...
June 23, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Fei Geng, Jian-Lin Wu, Gui-Feng Lu, Zhi-Ping Liang, Zhuo-Li Duan, Xi Gu
Gliomas are highly malignant tumors, the most common of which are astrocytomas. A growing number of studies suggest that dysregulation of miRNAs is a frequent event contributing to the pathogenesis of gliomas. In this study, we found that over-expression of miR-132 inhibited cell proliferation and migration and triggered apoptosis, while knockdown of miR-132 showed opposite effects. PEA-15 was identified as a direct target of miR-132. Reintroduction of PEA-15 without 3'UTR region reversed the inhibitory effects of miR-132 on cell proliferation, migration, and apoptosis...
September 2016: Journal of Neuro-oncology
Martina Maywald, Lothar Rink
PURPOSE: The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. METHODS: Cell proliferation and pro-inflammatory cytokine production were monitored by [(3)H]-thymidine proliferation assay and ELISA, respectively...
June 3, 2016: European Journal of Nutrition
Anjali Somal, Irfan A Bhat, Indu B, Sriti Pandey, Bibhudatta S K Panda, Nipuna Thakur, Mihir Sarkar, Vikash Chandra, G Saikumar, G Taru Sharma
The present study was conducted with an objective of isolation, in vitro expansion, growth kinetics, molecular characterization and in vitro differentiation of fetal adnexa derived caprine mesenchymal stem cells. Mid-gestation gravid caprine uteri (2-3 months) were collected from abattoir to derive mesenchymal stem cells (MSCs) from fetal adnexa {amniotic fluid (cAF), amniotic sac (cAS), Wharton's jelly (cWJ) and cord blood (cCB)} and expanded in vitro. These cultured MSCs were used at the 3rd passage (P3) to study growth kinetics, localization as well as molecular expression of specific surface antigens, pluripotency markers and mesenchymal tri-lineage differentiation...
2016: PloS One
Benjamin M Laitman, Linnéa Asp, John N Mariani, Jingya Zhang, Jia Liu, Setsu Sawai, Candice Chapouly, Sam Horng, Elisabeth G Kramer, Nesanet Mitiku, Hannah Loo, Natalie Burlant, Xiomara Pedre, Yuko Hara, German Nudelman, Elena Zaslavsky, Young-Min Lee, David A Braun, Q Richard Lu, Goutham Narla, Cedric S Raine, Scott L Friedman, Patrizia Casaccia, Gareth R John
Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails...
May 2016: PLoS Biology
Chris Fiore, Barak A Cohen
We investigated how interactions between pluripotency transcription factors (TFs) affect cis-regulation. We created hundreds of synthetic cis-regulatory elements (CREs) comprised of combinations of binding sites for pluripotency TFs and measured their expression in mouse embryonic stem (ES) cells. A thermodynamic model that incorporates interactions between TFs explains a large portion (72%) of the variance in expression of these CREs. These interactions include three favorable heterotypic interactions between TFs...
June 2016: Genome Research
Xiaoli Wang, Xiaoyan Li, Cuiping Huang, Lei Li, Hongmei Qu, Xiaoyan Yu, Huijie Ni, Qing Cui
Kruppel-like factors (KLFs) are a group of transcriptional regulators, being tumor-suppressive in various types of cancers, but not clear in human endometrial carcinoma (EC). We investigated the KLF-4 expression in both mRNA and protein levels in 29 EC specimens with RT-qPCR and Western blotting methods, and then to determine its promotion to Epithelial-to-mesenchymal transition (EMT) and proliferation of EC Ishikawa cells, via analyzing EMT-associated markers and via CCK-8 and colony forming assay. We found the downregulation of KLF-4 in the 29 EC specimens, correlating with the EC malignance...
April 20, 2016: Gynecological Endocrinology
Guo Yu, Fei Wu, Ersong Wang
BACKGROUND/AIMS: The transcription factor Krüppel-like factor (KLF) 8 plays important roles in tumorigenesis and tumor metastasis. However, the relationship between KLF8 and glioma cell chemoresistance is not known. METHODS: The effects of KLF8 on glioma cell proliferation, apoptosis and chemosensitivity to temozolomide (TMZ) were analyzed by Cell Counting Kit 8 assay and flow cytometry assay. A xenograft model was used to study the effect of KLF8 on tumor growth and sensitivity to TMZ...
2016: Cellular Physiology and Biochemistry
Gift Dineo Pule, Shaheen Mowla, Nicolas Novitzky, Ambroise Wonkam
BACKGROUND: The major therapeutic benefit of hydroxyurea, the only FDA-approved pharmacologic treatment for sickle cell disease (SCD), is directly related to fetal hemoglobin (HbF) production that leads to significant reduction of morbidity and mortality. However, potential adverse effects such as infertility, susceptibility to infections, or teratogenic effect have been subject of concerns. Therefore, understanding HU molecular mechanisms of action, could lead to alternative therapeutic agents to increase HbF with less toxicity...
March 2016: Clinical and Translational Medicine
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