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https://www.readbyqxmd.com/read/28716732/lysophosphatidic-acid-signaling-regulates-the-klf9-ppar%C3%AE-axis-in-human-induced-pluripotent-stem-cell-derived-neurons
#1
Tamotsu Tsukahara, Shuhei Yamagishi, Yoshikazu Matsuda, Hisao Haniu
Lysophosphatidic acid (LPA) is a lipid signaling molecule that plays several significant roles in the nervous system during development and injury. In this study, we differentiated human induced pluripotent stem cells (iPSCs) into neurons as an in vitro model to examine the specific effects of LPA. We demonstrated that LPA activates peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated nuclear receptor, as well as its cognate receptor LPA1 on human iPSC-derived neurons to enhance proliferation and neurite outgrowth...
July 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28641818/the-role-of-kr%C3%A3-ppel-like-factor-14-in-the-pathogenesis-of-atherosclerosis
#2
REVIEW
Wei Xie, Liang Li, Xi-Long Zheng, Wei-Dong Yin, Chao-Ke Tang
The Krüppel-like factor (KLF) family, as the SP/XKLF transcription factors, plays important roles in regulating the expression of genes required for the proper execution of important biological and pathological processes. Recent studies have demonstrated that KLF14, a member of the KLF family, participates in the initiation and progression of atherosclerotic cardiovascular disease (CVD). From the molecular function aspect, this review focuses on the impact of KLF14-mediated regulation in major atherosclerosis-related diseases and pathological processes, such as insulin resistance, type 2 diabetes, dyslipidemia, inflammation, obesity, metabolic syndrome, cell proliferation and differentiation...
June 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28600522/direct-competition-between-dna-binding-factors-highlights-the-role-of-kr%C3%A3-ppel-like-factor-1-in-the-erythroid-megakaryocyte-switch
#3
Laura J Norton, Samantha Hallal, Elizabeth S Stout, Alister P W Funnell, Richard C M Pearson, Merlin Crossley, Kate G R Quinlan
The Krüppel-like factor (KLF) family of transcription factors play critical roles in haematopoiesis. KLF1, the founding member of the family, has been implicated in the control of both erythropoiesis and megakaryopoiesis. Here we describe a novel system using an artificial dominant negative isoform of KLF1 to investigate the role of KLF1 in the erythroid/megakaryocytic switch in vivo. We developed murine cell lines stably overexpressing a GST-KLF1 DNA binding domain fusion protein (GST-KLF1 DBD), as well as lines expressing GST only as a control...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595633/effects-of-mechanical-stimulation-on-the-reprogramming-of-somatic-cells-into-human-induced-pluripotent-stem-cells
#4
Young Mi Kim, Yun Gyeong Kang, So Hee Park, Myung-Kwan Han, Jae Ho Kim, Ji Won Shin, Jung-Woog Shin
BACKGROUND: Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. However, few studies on their effects on induced pluripotent stem cells (iPSCs) have been published. METHODS: Human dermal fibroblasts were seeded onto flexible membrane-bottom plates, and infected with retrovirus expressing the four reprogramming factors OCT4, SOX2, KLF, and c-MYC (OSKM). The cells were subjected to equiaxial stretching (3% or 8% for 2, 4, or 7 days) and seeded on feeder cells (STO)...
June 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28583172/fluorescent-tagged-episomals-for-stoichiometric-induced-pluripotent-stem-cell-reprogramming
#5
Christopher E Schmitt, Blanca M Morales, Ellen M H Schmitz, John S Hawkins, Carlos O Lizama, Joan P Zape, Edward C Hsiao, Ann C Zovein
BACKGROUND: Non-integrating episomal vectors have become an important tool for induced pluripotent stem cell reprogramming. The episomal vectors carrying the "Yamanaka reprogramming factors" (Oct4, Klf, Sox2, and L-Myc + Lin28) are critical tools for non-integrating reprogramming of cells to a pluripotent state. However, the reprogramming process remains highly stochastic, and is hampered by an inability to easily identify clones that carry the episomal vectors. METHODS: We modified the original set of vectors to express spectrally separable fluorescent proteins to allow for enrichment of transfected cells...
June 5, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28545072/effect-of-vitamin-d-on-endothelial-progenitor-cells-function
#6
Yoav Hammer, Alissa Soudry, Amos Levi, Yeela Talmor-Barkan, Dorit Leshem-Lev, Joel Singer, Ran Kornowski, Eli I Lev
BACKGROUND: Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD) and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system...
2017: PloS One
https://www.readbyqxmd.com/read/28463968/differential-microrna-expression-in-human-placentas-of-term-intra-uterine-growth-restriction-that-regulates-target-genes-mediating-angiogenesis-and-amino-acid-transport
#7
Shanthie Thamotharan, Alison Chu, Katie Kempf, Carla Janzen, Tristan Grogan, David A Elashoff, Sherin U Devaskar
Placental insufficiency leading to intrauterine growth restriction (IUGR) demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that express biological function. To this end, we initially undertook microarrays targeting microRNAs in a small sub-set of placentas of appropriate (AGA) versus small for gestational age (SGA) weight infants, and observed up-regulation of 97 miRs and down-regulation of 44 miRs in SGA versus AGA...
2017: PloS One
https://www.readbyqxmd.com/read/28456933/genetic-deletion-of-kr%C3%A3-ppel-like-factor-11-aggravates-ischemic-brain-injury
#8
Xuelian Tang, Kai Liu, Milton H Hamblin, Yun Xu, Ke-Jie Yin
Krüppel-like factors (KLFs) belong to the zinc finger family of transcription factors, and their function in the CNS is largely unexplored. KLF11 is a member of the KLF family, and we have previously demonstrated that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs recruitment of KLF11 as its critical coactivator. Here, we sought to determine the role of KLF11 itself in cerebrovascular function and the pathogenesis of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was performed in KLF11 knockout and wild-type control mice, and brain infarction was analyzed by TTC staining...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28454392/klf7-overexpression-in-human-oral-squamous-cell-carcinoma-promotes-migration-and-epithelial-mesenchymal-transition
#9
Xiaojun Ding, Xinhao Wang, Yiming Gong, Hong Ruan, Yang Sun, Youcheng Yu
Krüppel-like factor 7 (KLF7) is a member of the KLF family of zinc finger transcription factors, and was the first KLF cloned using complementary DNA and polymerase chain reaction (PCR) techniques with human vascular endothelial cells as a template. In addition, KLF7 is known as the ubiquitous Krüppel-like factor, as it is widely expressed in numerous human tissues at low levels. In the present study, the function of KLF7 in migration and epithelial-mesenchymal transition (EMT), which are associated with tumor progression, was investigated in human oral squamous cell carcinoma (OSCC) cells...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28424532/stemness-and-differentiation-potential-recovery-effects-of-sinapic-acid-against-ultraviolet-a-induced-damage-through-the-regulation-of-p38-mapk-and-nf-%C3%AE%C2%BAb
#10
Young Sun Hwang, See-Hyoung Park, Mingyeong Kang, Sae Woong Oh, Kwangseon Jung, Yong Seek Park, Jongsung Lee
Ultraviolet A (UVA) irradiation exerts negative effects on stemness and differentiation potential of stem cells. This study aimed to explore the effect of sinapic acid on UVA-irradiation-induced damages to stemness and differentiation potential of human-adipose-tissue-derived mesenchymal stem cells (hAMSCs) and its UVA-antagonist mechanisms. Sinapic acid attenuated UVA-induced reduction in the proliferative potential and stemness by upregulating OCT4, SOX2, and NANOG. In addition, sinapic acid significantly recovered UVA-induced reduction in expression level of hypoxia-inducible factor (HIF)-1α...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423541/rna-sequencing-analysis-reveals-protective-role-of-kruppel-like-factor-3-in-colorectal-cancer
#11
Xiaohong Wang, Zhonghua Jiang, Yu Zhang, Xiang Wang, Li Liu, Zhining Fan
The Kruppel-like factor (KLF) family of transcription factors plays an important role in embryonic formation and cancer progression. This study was performed to determine the clinical importance of the KLF family in colorectal cancer (CRC). In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were used to comprehensively study the role of the KLF family in CRC. The results were then further validated using an in-house cohort (n=194). Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407733/the-kr%C3%A3-ppel-like-factor-9-cistrome-in-mouse-hippocampal-neurons-reveals-predominant-transcriptional-repression-via-proximal-promoter-binding
#12
Joseph R Knoedler, Arasakumar Subramani, Robert J Denver
BACKGROUND: Krüppel-like factor 9 (Klf9) is a zinc finger transcription factor that functions in neural cell differentiation, but little is known about its genomic targets or mechanism of action in neurons. RESULTS: We used the mouse hippocampus-derived neuronal cell line HT22 to identify genes regulated by Klf9, and we validated our findings in mouse hippocampus. We engineered HT22 cells to express a Klf9 transgene under control of the tetracycline repressor, and used RNA sequencing to identify genes modulated by Klf9...
April 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28366734/sp-and-klf-transcription-factors-in-digestive-physiology-and%C3%A2-diseases
#13
REVIEW
Chang-Kyung Kim, Ping He, Agnieszka B Bialkowska, Vincent W Yang
Specificity proteins (SPs) and Krüppel-like factors (KLFs) belong to the family of transcription factors that contain conserved zinc finger domains involved in binding to target DNA sequences. Many of these proteins are expressed in different tissues and have distinct tissue-specific activities and functions. Studies have shown that SPs and KLFs regulate not only physiological processes such as growth, development, differentiation, proliferation, and embryogenesis, but pathogenesis of many diseases, including cancer and inflammatory disorders...
March 30, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#14
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
June 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28281438/engineered-microvasculature-in-pdms-networks-using-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells
#15
Amogh Sivarapatna, Mahboobe Ghaedi, Yang Xiao, Edward Han, Binod Aryal, Jing Zhou, Carlos Fernandez-Hernando, Yibing Qyang, Karen K Hirschi, Laura E Niklason
In this study, we used a PDMS-based platform for the generation of intact, perfusioncompetent microvessel networks <i>in vitro</i>. COMSOL Multiphysics, a finite element analysis and simulation software package, was used to obtain simulated velocity, pressure, and shear stress profiles. Transgene-free human iPSCs were differentiated into partially arterialized endothelial cells (hiPSC-ECs) in 5 days under completely chemically defined conditions, using the small molecule GSK3β inhibitor CHIR99021 and thoroughly characterized for functionality and arteriallike marker expression...
March 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28261316/defective-lipid-metabolism-associated-with-mutation-in-klf-2-and-klf-3-important-roles-of-essential-dietary-salts-in-fat-storage
#16
Jun Ling, Christopher Brey, Megan Schilling, Farah Lateef, Zenaida P Lopez-Dee, Kristopher Fernandes, Kavita Thiruchelvam, Yi Wang, Kshitij Chandel, Kai Rau, Ranjit Parhar, Futwan Al-Mohanna, Randy Gaugler, Sarwar Hashmi
BACKGROUND: Dietary salts are important factors in metabolic disorders. They are vital components of enzymes, vitamins, hormones, and signal transduction that act synergistically to regulate lipid metabolism. Our previous studies have identified that Krüppel-like factor -3 (KLF-3) is an essential regulator of lipid metabolism. However, it is not known if KLF-2 also regulates lipid metabolism and whether KLF-2 and -3 mediate the effects of dietary salts on lipid metabolism. METHODS: In this study, we used klf mutants [homozygous klf-2 (ok1043) V and klf-3 (ok1975) II mutants] to investigate the role of dietary salts in lipid metabolism...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28239300/mir-7-inhibits-progression-of-hepatocarcinoma-by-targeting-klf-4-and-promises-a-novel-diagnostic-biomarker
#17
Weizhong Wu, Sanguang Liu, Yunfei Liang, Zegao Zhou, Xueqing Liu
BACKGROUND: MicroRNAs are 22-24 nt non-coding RNAs that bind to the 3' UTR of target mRNAs, thereby inducing mRNA degradation or inhibiting mRNA translation. Due to their implication in the regulation of post-transcriptional processes, the role of miRNAs in hepatocellular carcinoma (HCC) has been extensively studied. However, the function of miR-7 in HCC remains to be demonstrated. METHODS: 50 paired HCC tissues and matched peritumor tissues from patients were collected...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28218782/tumor-suppressive-role-of-kruppel-like-factor-4-klf-4-in-colorectal-cancer
#18
D H Xiu, Y Chen, L Liu, H S Yang, G F Liu
Kruppel-like factors (KLFs) are a group of transcriptional regulators that have recently been identified to exhibit tumor-suppressive function against various gastrointestinal cancers. The present study aims to investigate the expression patterns and prognostic value of KLF-4 in colorectal cancers (CRCs). KLF-4 levels in CRC tissues were examined via immunohistochemistry analysis, real-time quantitative polymerase chain reaction, and western blotting. The chi-square test was performed to evaluate the correlation between KLF-4 expression and the clinicopathological characteristics...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28179999/cancer-stem-like-cells-can-be-induced-through-dedifferentiation-under-hypoxic-conditions-in-glioma-hepatoma-and-lung-cancer
#19
Pan Wang, Wen-Wu Wan, Shuang-Long Xiong, Hua Feng, Nan Wu
Traditional studies have shown that transcription factors, including SOX-2, OCT-4, KLF-4, Nanog and Lin-28A, contribute to the dedifferentiation and reprogramming process in normal tissues. Hypoxia is a physiological phenomenon that exists in tumors and promotes the expression of SOX-2, OCT-4, KLF-4, Nanog and Lin-28A. Therefore, an interesting question is whether hypoxia as a stimulating factor promotes the process of dedifferentiation and induces the formation of cancer stem-like cells. Studies have shown that OCT-4 and Nanog overexpression induced the formation of cancer stem cell-like cells through dedifferentiation and enhanced malignancy in lung adenocarcinoma, and reprogramming SOX-2 in pancreatic cancer cells also promoted the dedifferentiation process...
2017: Cell Death Discovery
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
#20
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
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